Peripheral Neural Interface Via Nerve Regeneration to Distal Tissues

ABSTRACT

At least partial function of a human limb is restored by surgically removing at least a portion of an injured or diseased human limb from a surgical site of an individual and transplanting a selected muscle into the remaining biological body of the individual, followed by contacting the transplanted selected muscle, or an associated nerve, with an electrode, to thereby control a device, such as a prosthetic limb, linked to the electrode. Simulating proprioceptive sensory feedback from a device includes mechanically linking at least one pair of agonist and antagonist muscles, wherein a nerve innervates each muscle, and supporting each pair with a support, whereby contraction of the agonist muscle of each pair will cause extension of the paired antagonist muscle. An electrode is implanted in a muscle of each pair and electrically connected to a motor controller of the device, thereby simulating proprioceptive sensory feedback from the device.

RELATED APPLICATION(S)

This application claims the benefit of U.S. Provisional Application No.61/894,040, filed on Oct. 22, 2013 and U.S. Provisional Application No.62/019,266, filed on Jun. 30, 2014. The entire teachings of the aboveapplication(s) are incorporated herein by reference.

BACKGROUND OF THE INVENTION

Recent advances in prosthetic limbs include the provision of multipledegrees of freedom as well as powered actuators that have the potentialto provide substantially greater functionality than the passive devicesthat existed just a decade ago. Despite these engineeringaccomplishments, developers still struggle with the issue of how toprovide the prosthesis user with methods for coordinating thesimultaneous control of all of the joints that are involved with, forexample, object manipulation in the upper extremity case, or standingand walking in the lower extremity case. This deficit was first apparentfor upper extremity prostheses, which now can provide elbow function,wrist rotation, and hand opening and closing. Today's commerciallyavailable, upper-extremity prosthetic controllers make use of the EMGactivity (electro-myographic activity generated by muscle contraction)of functional native muscles that are present in the amputee's residuallimb. This approach allows for proportional control with minimalexecution delay. When the EMG activity used for prosthetic controlarises from a pair of antagonistic muscles that would normally move thehomologous biological joint (e.g., the biceps and triceps controllingflexion and extension, respectively, of the prosthesis elbow joint), theneurally controlled EMG commands are completely intuitive and thus easyto master.

However, more commonly in practice, the same set of EMG signal sourcesare used to control additional prosthetic joints, and this requires thatthe command sources be switched among the assigned joints in a serialmanner. The resulting motion for most activities is thus awkward, timeconsuming, and tedious, since it breaks up any compound arm and handmovement into serial positioning steps, resulting in poor utilization ofpowered prostheses. In the lower extremity, powered ankle and kneejoints are just becoming available to the general population. However,commercial lower-extremity prostheses typically do not utilize EMG as asource of control signals. Artificial sensory and computational systemshave been demonstrated to provide some degree of control over ankle andknee flexion and extension for powered leg prostheses (E. C.Martinez-Villalpando and H. M. Herr, “Agonist-antagonist active kneeprosthesis: A preliminary study in level-ground walking,” Journal ofRehabilitation Research & Development (JRRD), vol. 46, no. 3, pp.361-73, 2009; S. Au, J. Weber, and H. M Herr, “Powered Ankle-FootProsthesis Improves Walking Metabolic Economy,” IEEE Transactions onRobotics, vol. 25, no. 1, pp. 51-66, 2009; H. M. Herr and A. M.Grabowski, “Bionic ankle-foot prosthesis normalizes walking gait forpersons with leg amputation,” Proceedings of the Royal Society B, vol.279, no. 1728, pp. 457-464, February 2012; E. J. Rouse, L. M. Mooney, E.C. Martinez-Villalpando, and H. M. Herr, “A clutchable series-elasticactuator: design of a robotic knee prosthesis for minimum energyconsumption,” Proceedings of the IEEE International Conference onRehabilitation Robotics, 2013). It is well appreciated, however, thatthe next generation of devices should provide smooth, simultaneousvolitional-neural control over several degrees of freedom, such as theknee, ankle and subtalar joints. In that case, simultaneous control ofseveral degrees of freedom will require multiple sources of independent,reliable, and intuitive control that can best be obtained by interfacingwith the amputee's extrinsic neural control.

The efficacy of using an EMG-based neural activity approach forachieving simultaneous control of multiple prosthetic joints has beendemonstrated in principle by a technique now referred to as “TargetedMuscle Re-innervation,” or TMR (T. A. Kuiken, G. A. Dumanian, R. D.Lipschutz, L. A. Miller, K. A. Stubblefield, “The use of targeted musclereinnervation for improved myoelectric prosthesis control in a bilateralshoulder disarticulation amputee, Prosthetics and OrthoticsInternational, vol. 28, pp. 245-53, 2004; T. A. Kuiken, “Targetedreinnervation for improved prosthetic function,” Physical Medicine andRehabilitation Clinics of North America, vol. 17, no. 1, pp. 1-13,2006). For transhumeral prosthetic control, for example, TMR utilizesthe activity of all four of the arm trunk nerves. As a surgicalprocedure, each trunk nerve is mobilized from the brachial plexus, andeach nerve is anastomosed to a separate division of the pectoralis majormuscle of the chest. The nerves grow into and innervate their respectivenew muscle targets and can independently cause contractions of therespectively innervated pectoral muscle divisions. The four recordedmuscle signals can then be assigned to prosthetic elbow, wrist, and handfunctions according to the original natural hand control function ofeach of the translocated nerves. For example, hand closing is controlledby evoked EMG activity from the pectoral muscle division innervated bythe median nerve, and hand opening is controlled by EMG activity fromthe muscle division innervated by the radial nerve. Essentially, theoperator's brain performs the coordination of the prosthesis joints whena complex task is performed. Despite the laudable success of theoriginal and ensuing demonstrations, the TMR approach has a fewshortcomings; for instance, the native innervation of the pectoralmuscle (or other selected host muscle) must be removed so that thenormal activation of the host muscle by its native innervation does notinterfere with that by the transferred nerves. Having to eliminate thefunctionality of any native tissue for the greater good is not optimal.There are also some limitations regarding how far away a given nerve canbe moved in order to connect it to a suitable muscle target. Finally,the use of surface recorded EMG and contiguous muscle targets can leadto inconsistent signal amplitudes and objectionable channel crosstalk(T. A. Kuiken, M. M. Lowery, and N. S. Stoykov, “The effect ofsubcutaneous fat on myoelectric signal amplitude and cross-talk,”Prosthetics and Orthotics International, vol. 27, no. 1, pp. 48-54,2003). This last issue has been addressed by using a large array ofrecording sites and performing substantial pattern recognition tointerpret a user's intended movements unambiguously. Over time, however,it is still necessary to “re-tune” the system, which is a substantialinconvenience.

Therefore, there is a need for a method of reversing motor impairment ofa human limb, and of restoring at least partial function of a human limbthat overcomes or minimizes the above-referenced problems.

SUMMARY OF THE INVENTION

The invention generally is directed to a method of restoring at leastpartial function of a human limb, to reversing motor impairment of ahuman limb, to simulating proprioceptive sensory feedback from a device,and to simulate cutaneous sensory feedback from a device.

In one embodiment, the method of restoring at least a partial functionof the human limb includes surgically removing from a surgical site atleast a portion of an injured or diseased human limb from an individual,leaving intact at least one selected muscle from the damaged portion ofthe human limb, including at least one of blood vessels and nervesassociated with that portion of the at least one selected muscle. The atleast one selected muscle is transplanted into the remaining biologicalbody of the individual and the at least one transplanted selectedmuscle, or associated nerve, is contacted with an electrode, wherebysignals can be transmitted to and from at least one of the nerve and itsassociated transplanted muscle to thereby control a device linked to theelectrode and extending from the surgical site, thereby restoring atleast partial function of the human limb. Examples of suitable devicesfor use with the method of the invention include a prosthetic limb, anorthotic limb and an exoskeletal limb.

In a specific embodiment, and at least one patch of skin is dissected,wherein the patch of skin includes at least one nerve selected from thegroup consisting of an intact native sensory nerve and a newregenerative innervation nerve. The patch of skin is translocated onto anon-anatomical portion of the individual from which the limb wasremoved. The translocated patch is contacted with an external prostheticsocket of a prosthetic limb, the prosthetic socket including at leastone component that provides mechanical stimulation to the translocatedpatch of skin. In another embodiment, that further includes the steps ofcontacting the nerve of the patch of skin with a nerve cuff, wherein thenerve cuff is linked to a controller. The nerve is selectivelystimulated by actuating the nerve with the controller. In anotherembodiment, the nerve includes at least one sensory nerve selected fromthe group consisting of sural, saphenous, tibial, peroneal, median,ulnar, and radial nerves. In still one embodiment, contact in the nervesof the transplanted selected muscles with an electrode includesimplanting electrode on the epimysium of the selected muscle orintramuscularly in the selected muscles.

In another embodiment, the method of reversing impairment of a humanlimb includes transecting a nerve associated with the impairment of thelimb of an individual to thereby form proximal and distal ends of thetransected nerve. The proximal and distal ends of the transected nerveare placed into proximal and distal ends of a microchannel array,thereby causing the nerve to regenerate through the microchannel array.Sensory afferent information of the regenerated nerve is recorded usingsensing electrodes within a plurality of afferent microchannels of themicrochannel array. Motor efferent information is stimulated to provideefferent motor stimulus to the nerve using stimulating electrodes withinthe plurality of efferent microchannels of the microchannel array. Thestimulating electrodes are electrically connected to a motor controllerof a device. The sensing electrodes are electrically connected a sensorycontroller of the device, wherein the sensor controller is linked to atleast one sensor of the biological limb that detects application of atleast one of position, velocity, acceleration, and force of thebiological limb, and whereby the sensory controller transmits detectionof the position, velocity, acceleration, and force of the biologicallimb to the motor controller, and whereby the motor controller applieselectrical stimulation via the stimulating electrodes, thereby reversingimpairments of the human limb.

In still another embodiment, the invention is directed to a method ofrestoring at least partial function of the human limb of an individualthat includes dissecting at least one patch of skin from individual,translocating the patch of skin onto a non-anatomical portion of theindividual, wherein the skin patch includes at least one nerve selectedfrom the group consisting of an intact native nerve and a newregenerative innervation nerve, and contacting the translocated skinpatch with an external device, the device including at least onecomponent that provides mechanical stimulation to the translocated skinpatch, thereby restoring at least partial function of the human limb.

In still another embodiment, the method of the invention includesreversing the impairment of an amputated limb, including inserting adistal end of at least one transected nerve of an amputated limb into aproximal end of a microchannel array, placing at least one member of thegroup consisting of skin and muscle end organ at the distal end of themicrochannel array, thereby causing the nerve to regenerate through themicrochannel array and to innervate the at least one end organ. Efferentmotor information of the regenerated nerve is recorded using sensingelectrodes within a plurality of afferent microchannels of themicrochannel array. The regenerated nerve is stimulated with afferentsensory information using stimulating electrodes within a plurality ofafferent microchannels of the microchannel array. The sensing electrodesare electrically connected to a motor controller of a device. Thestimulating electrodes are electrically connected to a sensorycontroller of the device, wherein the motor controller is linked to atleast one sensor of the device that detects application of at least onemember selected from the group consisting of position, velocity,acceleration, and force of the device, and whereby the motor controllertransmits detection of the position, velocity, acceleration, and forceby applying electrical stimulation via the stimulating electrodes,thereby providing the individual with a sensation simulating sensoryfeedback from the device, and reversing impairment of the amputatedlimb.

In yet another embodiment of the invention, the method includessimulating proprioceptive sensory feedback from a device, including thesteps of the mechanically linking at least one pair of agonist andantagonist muscles, wherein a nerve innervates each muscle. The at leastone pair of agonist and antagonist muscles are supported with a support,whereby contraction of the agonist muscle of each pair will causeextension of the paired antagonist muscle. At least one electrode isimplanted in at least one muscle of each pair, and the at least oneelectrode is electrically connected to a motor controller of the device,thereby stimulating proprioceptive sensory feedback from the device.

In another embodiment, the invention is a method for simulatingcutaneous sensory feedback from the device, including steps of excisinga skin segment from a biological body part of an individual, the skinsegment including at least one of a native nerve and a regenerativenerve supply. The skin segment is linked to at least one muscle having anerve supply. An electrode is implanted in the at least one muscle. Theskin segment and actuator muscle are supported on a support. The atleast one electrode is electrically connected to a sensory controller ofa device, wherein the controller is linked to a sensor of the devicethat detects application of at least one of stress, strain, contact,pressure and sheer at the device, and whereby the controller transmitsdetection of the stress, strain, contact, pressure or sheer bycontracting the actuator muscle within electrical stimulation via theelectrode, thereby stretching the mechanoreceptor of the skin segmentand providing the individual with a sensation stimulating cutaneoussensory feedback from the device.

This invention has many advantages. For example, Applicants' claimedinvention provides a strategy for clinicians to follow when planning anamputation procedure so that the possibility to later obtain enhancedprosthetic control is maximized. Specifically, in the case of limbamputation, this strategy may include deriving multiple independentelectrical signals, such as electromyographic signals, and neuralrecorded signals to command powered actuators within an externalprosthesis. Further, artificial sensory information may be provided fromthe externally-controlled limb prosthesis back to the amputee bymechanically stimulating relocated cutaneous tissues salvaged from theamputated limb or, alternatively, bioelectrically activating sensorynerve fibers in the residual limb using a novel neural interface design.

The surgical reconstruction methodology and implantable system of theinvention significantly increases the potential for natural neuralcontrol of prostheses, such as artificial limbs and functionalelectrical stimulation devices. The system utilizes the neural activitywithin the residual biological limb generated in the peripheral nervesand/or the electromyographic activity generated through muscle tissueactivation. Such nerve and muscle tissues may be native to the residuallimb, or they may be relocated to the residual limb through a pluralityof surgical manipulations. Such manipulations may include free musclegrafts or pedicle muscle grafts, which may include intact attachednerves and/or vasculature. Additionally, the musculature could bederived from transplanted muscle precursor cells or cultured muscletissue. For amputation limb patients, the system includes means torecord one or multiple independent channels of neural motor activitythat can control the various degrees of freedom present in advancedpowered prosthetic limbs. Further, the method of the invention providesfor the possibility of sensory information input from a controlledexternal prosthesis back into the nervous system. With regard tocutaneous sensory feedback, this can be by electrically activatingsensory nerves through a nerve cuff and/or microchannel array directly,or by applying mechanical stimulation to the native skin of the residuallimb or other cutaneous tissue, such as fingertip skin, that has beenrelocated by a grafting procedure to the residual limb.

The invention also includes means to provide proprioceptive feedback tothe amputee. This can be achieved through direct electrical activationof muscle and tendon afferent nerve fibers using the microchannel array.The invention also allows relocated antagonistic muscle pairs tomechanically interact with each other in a reciprocal push-pull fashion,just as would occur if the agonist/antagonist muscle pair were attachedto the opposing sides of a joint. This approach allows the muscleproprioceptive endings that are intrinsic to those muscles to beactivated by a normal stretch stimulus that occurs with intact musclesoperating around the same joint.

The invention also has application in neural interface technology, suchas for spinal cord lesion patients, stroke patients and other motorimpairment disabilities, in that sensory information from the distalbiological limb, or biological member, can be recorded from channelswithin an implanted microchannel array. Such signals can then beemployed in an artificial feedback algorithm to then stimulate distallimb muscles through motor channels within the same microchannel array,or an alternate microchannel array.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be apparent from the following more particulardescription of example embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingembodiments of the present invention.

FIG. 1 is a schematic representation of surgical removal of a portion ofan injured or diseased human limb, in outline, leaving intact a portionof selected muscles, including blood vessels and nerves associated withthat portion of the selected muscles, according to one embodiment of themethod of the invention.

FIG. 2A is a schematic representation of transplantation of the selectedmuscles of FIG. 1 to a surgical site of the individual where the limbwas removed according to the embodiment of the method of the inventionof FIG. 1.

FIG. 2B is a schematic representation of implanting an electrode on tothe epimesial surface of the selected muscles of FIG. 2A.

FIG. 3 is a schematic representation of providing electrical isolationbetween relocated and native muscles.

FIG. 4 is a schematic representation of surgical removal of a portion ofan injured or diseased human limb, in outline, leaving intact a portionof selected muscles and selected glabrous skin patches, including bloodvessels and nerves associated with those portions of the selectedmuscles and glabrous skin patches, according to another embodiment ofthe invention.

FIG. 5A is a schematic representation of grafting a patch of skin intothe individual shown in FIG. 4 at the surgical site where the limb orlimb portion was removed according to the embodiment of the invention ofFIG. 4.

FIG. 5B is a cross section of the patch of skin grafted into theindividual as shown in FIG. 5A.

FIG. 6A is a first representation of contacting a grafted patch of skintransplanted from finger pads of an individual with an externalprosthetic socket of a prosthetic limb according to another method ofthe invention, wherein the prosthetic socket includes at least oneactuator component that provides mechanical stimulation of the graftedpatch of skin.

FIG. 6B is a second, subsequent representation of contacting a graftedpatch of skin transplanted from finger pads of an individual with anexternal prosthetic socket of a prosthetic limb according to anothermethod of the invention, wherein the prosthetic socket includes at leastone actuator component that provides mechanical stimulation of thegrafted patch of skin.

FIG. 6C is a schematic representation of a segment of the prosthetic andthe actuator shown in FIG. 6B.

FIG. 6D is a schematic representation of the prosthetic of FIG. 6C afteractuation of the actuator.

FIG. 7A is a schematic representation of contacting native sensoryinnervation of a skin patch with nerve cuffs, wherein the nerve cuffsare linked to a controller, and selectively stimulating the nativesensory innervation by actuating the nerve cuffs with the controller,according to yet another embodiment of the invention.

FIG. 7B is another schematic representation of the embodiment of theinvention shown in FIG. 7A, showing placement of implanted electronicsand the nerve cuffs of FIG. 7A.

FIG. 8A is a schematic representation of transecting a nerve of a limbof an individual to thereby form proximal and distal ends of thetransected nerve, and of placing the proximal and distal ends of thetransected nerve in a microchannel array, the microchannel arrayincluding a bidirectional interface that records afferent information ofthe nerve and that provides efferent stimulus to the nerve, once thenerve has regenerated in the microchannel array, according to anotherembodiment of the method of the invention.

FIG. 8B is a representation of one embodiment of placement of themicrochannel array at the surgical site of an individual and relativelocation of a prosthetic limb controlled by the microchannel array.

FIG. 9 is a schematic representation of the microchannel array of FIGS.8A and 8B, wherein nerve fibers from a nerve proximal to an amputationsite grow through the array and connect to target tissue nerves arrangedon the other side of the array.

FIG. 10 is a schematic representation of another embodiment of themicrochannel array of FIGS. 8A and 8B, wherein nerve fascicles from aproximal nerve in the residual limb are separated by function and placedinto different channels of the array, whereby the fascicles regeneratethrough the array and reconnect to the native innervation of appropriatetarget tissues that have been relocated and arranged on the other sideof the array.

FIG. 11A is a schematic representation of still another microchannelarray employed by at least one embodiment of the method of theinvention, wherein nerves in a paralyzed limb affected by a motorimpairment disability (e.g., spinal cord lesion) are transected, andmicro-channel array devices are placed between the proximal and distalnerve stumps whereby, after nerve regeneration, the limb may becontrolled via artificial muscle stimulations using sensory recordingsfrom channels within the implanted array devices.

FIG. 11B is a representation of placement of the microchannel array ofFIG. 11A.

FIG. 12 is a schematic representation of one embodiment of a method forfabricating a three-dimensional array suitable for use by at least oneembodiment of the method of the invention.

FIG. 13A is an exploded view of one embodiment of a three-dimensionalmicrochannel array suitable for use by at least one method of theinvention.

FIG. 13B is a perspective view of the assembled three-dimensionalmicrochannel array of FIG. 13A.

FIG. 14 is schematic representation of supporting at least one pair ofagonist and antagonist muscles by one embodiment of the method of theinvention, whereby contraction of the agonist muscle of each pair willcause extension of the paired antagonist muscle, and whereby theagonist-antagonist muscle pair provide proprioceptive information aboutmovement and impedance via activity generated from the muscle spindleand tendon afferents of the agonist-antagonist muscle pair.

FIG. 15 is a schematic representation of a proprioceptive muscleRegenerative Peripheral Nerve Interface (Pro-m-RPNI) comprising anagonist-antagonist muscle pair series secured to bone or anotherbiological structure at either end, suitable for employment in oneembodiment of the method of the invention.

FIG. 16 a schematic representation of a linear Pro-m-RPNI in which thenative tendon-bone junction at either end of the series is preserved toenable attachment to a synthetic structure.

FIG. 17 is a schematic representation of a Pro-m-RPNI secured about asynthetic spool shown comprising: 1) a synthetic spool; 2) an agonistmuscle; 3) an agonist motor/afferent nerve; 4) an agonist electrode forelectromyographic sensing and functional electrical stimulation; 5)agonist muscle spindle fibers; 6) an agonist Golgi tendon organ; 7) anantagonist muscle; 8) an antagonist motor/afferent nerve; and 9) anantagonist electrode for electromyographic sensing and functionalelectrical stimulation.

FIG. 18 is a schematic representation of a unidirectional CutaneousSensory RPNI (Cut-s-RPNI).

FIG. 19 is a schematic representation of a multi-directional Cut-s-RPNIaround a synthetic sphere that is suitable for use in at least onemethod of the invention.

FIG. 20 is a schematic representation of a Pro-m-RPNI and a Cut-s-RPNIintegrated with a bionic prosthesis.

DETAILED DESCRIPTION OF THE INVENTION

A description of example embodiments of the invention follows.

The invention generally is directed to a method of restoring at leastpartial function of a human limb, to reversing motor impairment of ahuman limb, to simulating a proprioceptive sensory organ for a humanlimb or organ, and to simulating a cutaneous sensor organ for a humanlimb or organ of an individual.

One goal of amputation surgery is to use the muscle tissues at thedistal end of the residual limb to provide an appropriate cone shape tothe limb so that a prosthetist will be able to fit a socket to the limbthat will receive an artificial prosthesis. The distal ends of amputatednerves are usually buried into fat tissue or deep into the residual limbto provide protection to them from mechanical stimulation, which mightotherwise cause painful sensations.

One critical innovation that is described herein is a strategy forclinicians to follow when planning an amputation procedure so that thepossibility to later obtain enhanced prosthetic control is maximized. Inthe case of limb amputation, this strategy would include derivingmultiple independent EMG signals and neural recorded signals to commandpowered actuators within an external prosthesis. A further innovation isto provide for artificial sensory information from the externalcontrolled limb prosthesis back to the amputee by mechanicallystimulating relocated cutaneous tissues salvaged from the amputatedlimb, or by electrically activating sensory nerve fibers in the residuallimb using a novel neural interface design.

EMG Acquisition Using Skin Surface Electrodes—

Myo-electric powered upper extremity prostheses have traditionallyemployed surface recording techniques to sense EMG activity. Typically,EMG signals are registered using small metal button-shaped electrodesthat are mounted within the shell of the prosthesis socket so that theycontact the skin overlying the muscles selected for the control tasks.Other electrode materials are possible, including conductive polymers,metal-impregnated woven fabrics, and carbon composites, for example.

To achieve an acceptable signal to noise ratio (SNR) and excludeunwanted biosignals, such as the electrocardiogram, a bi-polar recordingconfiguration generally is recommended (C. J. De Luca, DelSys Inc.“Surface Electromyography: Detection and Recording,” DelSys Inc.,Tutorial, 2002), although other configurations, such as a tri-polarrecording, configuration could be employed.

It is also possible to cover an area of skin with an array of electrodeelements and combine their outputs in arbitrary combinations in order toimprove the SNR or to improve the ability to isolate the activity ofindividual muscles. Surface EMG acquisition has the advantage that it isnon-invasive and the electrodes can be relocated if desired. There are,however, several disadvantages associated with surface recording. Theseinclude low signal amplitudes and variability in the signal amplitudecaused by perspiration, changes in the thickness of the subcutaneous fatbetween the electrode and the underlying muscle, and movement of theelectrodes relative to the recorded muscle from rotation of the limb andstretching of the skin. Other serious limitations of surface recordingare contamination of the signal from activity in neighboring muscles andthe inability to record selectively from muscles that are notsuperficial.

EMG Acquisition Using Implanted Sensors—

The limitations imposed with surface recording of EMG activity canlargely be mitigated by securing electrodes directly onto the epimesialsurface of the muscle or by placing penetrating electrodes into themuscle tissue itself. Implantable epimesial electrodes and coiled wireintramuscular electrodes developed for electrical stimulation of muscle,but suitable for recording EMG activity, are known in the art.Variations of these designs could include bi-filar intramuscular coiledwire electrodes and epimesial electrodes, (P. A. Grandjean and J. T.Mortimer, “Recruitment properties of monopolar and bipolar epimysialelectrodes,” Annals of Biomedical Engineering, vol. 14, no. 1, pp.53-66, 1986), which contain additional contact sites attached to acommon backing.

An example of a suitable implantable device that acquires EMG activityfrom residual limb muscles for the control of powered artificial limbsis the BION2™ powered artificial limb, developed by the Alfred MannFoundation which consists of a ceramic cylinder approximately 3 mmdia.×15 mm long that can be installed into a muscle by loading it intothe lumen of a hypodermic needle and then withdrawing the needle,leaving the sensor behind in the tissue. Each sensor is a stand-alonedevice capable of recording electrical activity by means of electrodecontacts that are located at the ends of the cylinder. Each sensor isaddressable so that its registered data can be telemetered to a centralreceiver terminal located in the shell of the prosthesis. Power for theimplanted sensors is supplied via an RF link from a single transmittercoil that is located around the circumference of the prosthesis shelland communicates with all of the BION2™ devices that are implanted inthe tissues that lie beneath the coiled region. An example applicationof these sensors is in an Implantable Myoelectric Sensor (IMES) System,described in R. F. Weir, P. R. Troyk, G. A. DeMichele, D. A. Kerns, J.F. Schorsch, and H. Maas, “Implantable myoelectric sensors (IMESs) forintramuscular electromyogram recording,” IEEE Transactions on BiomedicalEngineering, vol. 56, no. 1, pp. 159-171, 2009.

Another implementation of an implantable EMG controller system includesa centralized processor package that resembles a “pacemaker” module. Ithas several paired leads that extend from the processor out toindividual muscles. Each set of leads terminates in a set ofbutton-shaped electrodes that are sutured to the epimesium of themuscles used to control the actuators of a powered prosthesis. Morerecently, a smaller device has been developed that includes an ASICdedicated specifically for recording and transmitting EMG activity. (B.D. Farnsworth, Wireless Implantable EMG Sensing Microsystem, Mastersthesis, Case Western Reserve University, August 2010).

Direct Interfacing to Peripheral Nerves—

It has long been recognized that superior prosthetic limb control couldbe obtained if it was possible to establish the means to achieve abi-directional interface with the peripheral nerves present in theresidual limb. Researchers have applied several different approaches toachieve this goal, (K. Yashida and R. Riso, “Peripheral nerve recordingelectrodes and techniques,” in Neuroprostheses in Theory and Practicevol. 2, K. W. Horch and G. S. Dhillon, Eds. Hakensack, N.J.: WorldScientific, 2004, pp. 683-744), including various designs ofcircumferential nerve cuffs (e.g., Huntington Helix, W. F. Agnew, D. B.McCreery, T. G. H. Yuen, and L. A. Bullara, “Histologic and physiologicevaluation of electrically stimulated peripheral nerve: Considerationsfor the selection of parameters,” Annals of Biomedical Engineering, vol.17, pp. 39-60, 1989); self sizing spiral cuffs (G. G. Naples, J. T.Mortimer, A. Scheiner, and J. D. Sweeney, “A spiral nerve cuff electrodefor peripheral nerve stimulation,” IEEE Transactions on BiomedicalEngineering, vol. 35, no. 11, pp. 905-916, 1988); multi-polar cuffs (C.Veraart, W. M. Grill, and J. T. Mortimer, “Selective control of muscleactivation with a multipolar nerve cuff electrode,” IEEE Transactions onBiomedical Engineering, vol. 40, no. 7, pp. 640-653, 1993; M. Schuettlerand T. Stieglitz, “18polar hybrid cuff electrodes for stimulation ofperipheral nerves,” in Proceedings of the International FunctionalElectrical Stimulation Society, Aalborg, Denmark, pp. 265-268, 2000) andcuffs with multiple chambers, (J. A. Hoffer, Y. Chen, K. Strange, and P.R. Christensen, “Nerve cuff having one or more isolated chambers,” U.S.Pat. No. 5,824,027 A, Oct. 20, 1998). Such “wrap around” cuffs designshave the inherent limitation that it is difficult to record from or tostimulate nerve fascicles that are not located on the surface of thenerve and that may lie deep within the trunk nerve. One cuff design actsto mitigate this problem by flattening and hence reshaping the nerve toforce fascicles to align side by side, thereby providing more equalaccess to all fascicles of the nerve, (D. Tyler and D. Durand, “Flatinterface nerve electrode and a method for use,” U.S. Pat. No. 6,456,866B1, Sep. 24, 2002).

Penetrating Interfascicular Electrodes and Micro-Electrode Arrays—

Efforts to achieve better fiber specificity for recording andstimulation have led to the development of an array of needle-likeelectrodes (resembling a brush) having 100 contact points that isinserted transversely into the peripheral nerve. This approach allowsnearly single unit specificity, similar to what is achieved usingindividual micro-electrodes. Despite this inherent advantage, thus far,electrode stability remains a major issue, because the electrode contactpoints tend to be extruded away from their original nerve fiberlocations over time, (A. Branner and R. A. Normann, “A multielectrodearray for intrafascicular recording and stimulation in sciatic nerve ofcats,” Brain Research Bulletin, vol. 51, no. 4, pp. 293-306, 2000).

Another strategy to achieve high fiber specificity involves drawing finewire or conductive polymer filaments into the nerve, essentially using asewing technique for implantation. Each filament contains a small zonethat is an electrode contact site and is capable of recording orstimulating nearby nerve fibers. Again, while this approach has shownthe ability to isolate individual nerve fiber activity, over time thecontact site moves relative to the nerve fibers, so that long termstability so far typically is not adequate for clinical use (M. S.Malagodi, K. W. Horch, and A. A. Schoenberg, “An intrafascicularelectrode for recording of action potentials in peripheral nerves,”Annals of Biomedical Engineering, vol. 17, pp. 397-410, 1989; K. Yoshidaand R. B. Stein, “Characterization of signals and noise rejection withbipolar longitudinal intrafascicular electrodes,” IEEE Transactions onBiomedical Engineering, vol. 46, no. 2, pp. 226-234, 1999; and S. M.Lawrence, J. O. Larsen, K. W. Horch, R. Riso, and T. Sinkjaer,“Long-term biocompatibility of implanted polymer-based intrafascicularelectrodes,” Journal of Biomedical Materials Research, vol. 63, no. 5,pp. 501-506, 2002). Another severe limitation is that the number offibers that can be “sewn” into a given nerve is very small (˜perhaps10), and this can result in a very poor sampling of the potentialinformation that is available in a peripheral nerve.

Regeneration-Based Nerve Interfaces—

Regardless of advances made in cuff-based nerve interface designs, theextent of specificity that can be obtained for stimulating and recordingis still extremely limited. Much better selectivity can be achieved ifthe fibers at the end of an amputated nerve are allowed to grow into astructure that consists of an array of micro-channels. Experience hasshown that nerve fibers will invade each of the channels, and thiseffectively separates the nerve into small numbers of fibers that arelikely to share some commonalities in function. Thus, a singlemicro-channel can include motor fibers that originally subserved asingle muscle rather than multiple muscles. Similar benefits apply withregard to sensory nerve fibers, where the contents of a singlemicro-channel can include of sensory fibers that are of a single sensorymodality, such as light touch or sustained pressure, or fibers that havereceptive fields restricted to a small perceived locus on the phantomlimb.

The development of regeneration electrodes began with “sieve” typedesigns that were disks with an array of fine caliber holes or slotsdrilled through them, (see, e.g., D. J. Edell, “A peripheral nerveinformation transducer for amputees: long-term multichannel recordingsfrom rabbit peripheral nerves,” IEEE Transactions on BiomedicalEngineering, vol. 33, no. 2, pp. 203-214, 1986; G. T. A. Kovacs, C. W.Storment, and J. M. Rosen, “Regeneration microelectrode array forperipheral nerve recording and stimulation,” IEEE Transactions onBiomedical Engineering, vol. 39, no. 9, pp. 893-902, 1992; R. M.Bradley, R. H. Smoke, T. Akin, and K. Najafi, “Functional regenerationof glossopharyngeal nerve through micromachined sieve electrode arrays,”Brain Research, vol. 594, no. 1, pp. 84-90, 1992; R. M. Bradley, X. Cao,T. Akin, and K. Najafi, “Long term chronic recordings from peripheralsensory fibers using a sieve electrode array,” Journal of NeuroscienceMethods, vol. 73, no. 2, pp. 177-186, 1997; T. Akin, K. Najafi, R. H.Smoke, and R. M. Bradley, “A micromachined silicon sieve electrode fornerve regeneration applications,” IEEE Transactions on BiomedicalEngineering, vol. 41, no. 4, pp. 305-313, 1994; Navarro, S. Calvet, F.J. Rodriguez, T. Stieglitz, C. Blau, M. Buti, E. Valderrama, and J. U.Meyer, “Stimulation and recording from regenerated peripheral nervesthrough polyimide sieve electrodes,” Journal of the Peripheral NervousSystem, vol. 3, no. 2, pp. 91-101, 1998; L. Wallman, Y. Zhang, T.Laurell, and N. Danielsen, “The geometric design of micromachinedsilicon sieve electrodes influences functional nerve regeneration,”Biomaterials, vol. 22, no. 10, pp. 1187-93, 2001; and L. Wallman, A.Levinsson, J. Schouenborg, H. Holmberg, L. Montelius, N. Danielsen, andT. Laurell, “Perforated silicon nerve chips with doped registrationelectrodes: in vitro performance and in vivo operation,” IEEETransactions on Biomedical Engineering, vol. 46, no. 9, pp. 1065-73,1999). Such designs generally did not perform well because the electrodefaces were located on the flat surfaces of the disks (perpendicular tothe direction of nerve growth) and because the sharp edges of the holescould cut the nerve fibers that grew through the device. A moresatisfactory design was a disk that was thick enough so that theelectrode faces could be placed within lengthened holes, referred to asmicro-channels. An example of early implementation of a micro-channelapproach was in the MIT Biomechatronics Research Group, in collaborationwith InnerSea Technology, where a bundle of 200 um ID polyimide tubingwas sheared to a length of 3 mm to form a micro-channel array. Sharpenedmetal microelectrodes were introduced into the lumen of some of thechannels so that neural recordings could be performed. The tibial nervein a rabbit model was transected, and then the proximal nerve stump wasallowed to grow into the implanted micro-channel array to form areconnection to the distal nerve stump in a nerve-to-nerve repair. Afterrecovery, it was demonstrated that neural activity could be recordedfrom the various array channels, and subsequent histological studiesshowed that the majority of the array channels contained regeneratednerve fibers and supporting vasculature (D. Edell, R. Riso, and H. Herr,“Bi-directional peripheral nerve interface for the control of poweredprosthetic limbs,” DARPA Contract N66001-05-C-8030, 2006). Furthermore,in separate experiments using a “Y” maze paradigm, in which regeneratingfibers were given a choice of growing into one of two chamberscontaining a small slice of either skin tissue or muscle tissue, it wasshown that such “target tissues” are useful in trying to achieve aseparation of motor efferent nerve fibers from sensory cutaneousafferent nerve fibers (D. Edell et al.). These studies were subsequentlyreferenced as the basis for a patent submission that describes nerveregeneration based nerve interfacing (D. J. Edell and R. R. Riso, “Longterm bi-directional axon-electronic communication system,” U.S. patentapplication Ser. No. 11/629,257, filed on Jun. 15, 2005 and published onSep. 18, 2008 as U.S. 2008/0228240).

Subsequent developments of the micro-channel nerve interface strategyusing a rat amputated nerve model in other laboratories (J. J.Fitzgerald, S. P. Lacour, S. B. McMahon, and J. W. Fawcett,“Microchannels as axonal amplifiers,” IEEE Transactions on BiomedicalEngineering, vol. 55, no. 3, pp. 1136-1146, 2008; J. J. Fitzgerald, N.Lago, S. Benmerah, J. Serra, C. P. Watling, R. E. Cameron, E. Tarte, S.P. Lacour, S. B. McMahon, and J. W. Fawcett, “A regenerativemicrochannel neural interface for recording from and stimulatingperipheral axons in vivo,” Journal of Neural Engineering, vol. 9, no. 1,pp. 016010, 2012; and S. P. Lacour, J. J. Fitzgerald, N. Lago, E. Tarte,S. McMahon, and J. Fawcett, “Long micro-channel electrode arrays: anovel type of regenerative peripheral nerve interface,” IEEETransactions on Neural Systems and Rehabilitation Engineering, vol. 17,no. 5, pp. 454-60, 2009) have corroborated the hypothesis that atransected nerve will regenerate into a micro-channel structure and thatelectrodes placed within individual channels can record neural activitywith minimal cross-talk (signal leakage) between channels.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION First Embodiment

FIGS. 1, 2A and 2B are schematic representations of one embodiment ofthe method of the invention that includes the method of the restoring atleast partial function of a human limb. At least a portion 10 (shown inoutline) of an injured or diseased human limb 12 from an individual issurgically removed, leaving intact at least a portion of selectedmuscles 14 from the damaged portion of the human limb, including bloodvessels and nerves 16 associated with that portion of the selectedmuscles 14. The selected muscles are transplanted to a surgical site 18of the individual where the human limb was removed. The transplantedselected muscles 14 and associated nerves 16 are then contacted withelectrodes 20 (FIGS. 2A and 2B), whereby signals can be transmitted toand from nerves 16 at the transplanted muscles 14 to thereby control aprosthetic limb (not shown) that is linked to the electrodes and extendsfrom the surgical site 18.

A model for a transfemoral (above-the-knee) amputation is illustrated inFIG. 1, but it will be clear to those of ordinary skill in the art thatthis embodiment is more broadly applicable to any amputation surgery inwhich muscles from the distal (amputated) limb can be salvaged withtheir native nerve innervation intact and perhaps, when possible, theirnative vasculature. For example, this embodiment could be applied totranshumeral, transradial, and transtibial amputation procedures. Insuch procedures, muscles can be relocated to the portion of the limbthat is retained after the amputation surgery, providing new sources ofsignals, such as EMG signals, that can be harnessed for the control ofadvanced external devices, such as limb prostheses, orthoses orexoskeletons.

In a specific embodiment, using surface recording techniques, EMGsignals from both the native and re-located muscles are sensed fromelectrodes mounted in the prosthetic socket shell, where electrodescontact the skin overlying the targeted muscles. Alternatively, an IMESimplantable sensor, such as discussed earlier, is employed to measureand transmit the EMG signal from both native and re-located muscleswithin the residual biological limb post amputation surgery.

Listed below are examples of muscles that can be transferred to theresidual limb during a transfemoral amputation surgical procedure inorder to gain signals for the ankle and subtalar joint control of aprosthesis:

Tibialis anterior m.—ankle dorsiflexion and eversion

Gastronemius m.—ankle plantar flexion

Soleus m.—ankle plantar flexion

Posterior tibialis m.—ankle inversion

Peroneus Longus—eversion and plantar flexion of ankle

Additionally, this embodiment of the invention can be employed tocontrol actuation of toes. This can be achieved by employing EMG commandsignals recorded from, for example, the following leg muscles:

Flexor Digitorum longus—2^(nd) toe flexor

Extensor Digitorum longus—2^(nd) toe extensor

Flexor Hallucis longus—great toe flexor

Extensor Hallucis longus—great toe extensor

In the case of a transfemoral amputation, surface recording electrodescan be employed to register the activity of the residual limb's nativeknee flexor and extensor muscles, such as the quadriceps and hamstringmuscle groups, for the control of prosthetic knee extension and flexion,respectively. The knee joint is fundamentally a single degree of freedomjoint and can be controlled using a single flexor and extensor musclepair. Preferably, EMG command signal contributions from as many of theknee-controlling muscles as possible can be obtained so that theimpedance (stiffness and damping) of the knee joint in an advancedprostheses can be accurately modulated during ambulation and otherlower-extremity activities.

During surgery, viable muscles and their native innervation in theportion of the limb that will ultimately be amputated are dissected andpacked into the residual limb, as shown in FIGS. 2A and 2B. Nerves to atarget muscle can be mobilized by interfasicular dissection wherepossible or by freeing the entire trunk nerve and removing extraneousbranches to muscles that will not be re-located and used for prosthesiscontrol.

Depending on the positioning of the native and relocated musclesrelative to each other, it may be necessary to provide means toelectrically isolate some or all of the muscles to prevent electricalcross talk between the recording channels. Electrically isolating nativemuscle tissue has previously been discussed by Kuiken, who suggestedusing fat tissue or silicone sheeting to wrap portions of the nativemuscles and thus prevent the spread of objectionable action currentsbetween native muscles, (T. Kuiken, N. Stoykov, M. Lowery, and A.Taflove, “Finite element analysis of EMG signals to improve the controlof myoelectric prostheses,” in 10th World Conference of theInternational Society for Prosthetics and Orthotics, Glasgow, UK, 2001).Silicone is an acceptable material for this purpose because it is highlybiocompatible, easily molded into arbitrary shapes, and possesses a highdielectric constant. One possible scheme of providing electricalisolation between relocated and native muscles in the residual limb isdepicted in FIG. 3. During surgery, relocated muscles can be packed intoa multi-chamber silicone structure 21, which can be held in place bysutures to tissues or by attachment to bone in the residual limb. Such astructure can also help in preventing residual limb pain by padding theend of the residual bone, for example, and by mechanically shieldingrelocated nerve fibers from forces exerted to the exterior surfaces ofthe residual limb. Other materials or combinations of materials, such aslaminated structures, can be employed as well. This technique can beparticularly beneficial if specific stiffness properties are desired toreconstruct the residual limb to better accommodate the forces exertedagainst the tissues by the external prosthetic socket.

After surgery, EMG signals from the relocated muscles and any relevantnative residual limb muscles are sensed with surface electrodes mountedin the prosthesis socket so that the electrodes contact the skinoverlying the targeted muscles. These electrodes can also be mounteddirectly on the skin. Alternatively, implanted sensors such as the IMESdescribed previously could be employed to acquire the EMG controlsignals from native and relocated muscles.

The method of the invention described with reference to FIGS. 1, 2A and2B typically requires no nerve transection, or grafting, though suchadditions can be made if the amputation demands it (e.g. a small portionof the nerve to a target muscle is damaged).

Second Embodiment

FIGS. 4-6 are schematic representations of a second embodiment of amethod of the invention for restoring at least partial function of ahuman limb. Specifically, FIG. 4 is a schematic representation ofsurgical removal of a portion 22 (in outline) of an injured or diseasedhuman limb 24, in outline, leaving intact a portion of selected muscles26 and selected glabrous skin patches 28, including blood vessels andnerves 30 associated with those portions of the selected muscles 26 andglabrous skin patches 28, according to another embodiment of theinvention. Alternatively, or in addition, the nerve can be a newregernative innervation nerve. “New regenerative innervation nerve,” asthat term is employed herein, is a nerve that has regenerated or growninto muscle or skin cells. Similarly, an “end organ,” as that term isemployed herein, is a tissue body into which a nerve regenerates. Thus,a muscle body or a skin body into which a nerve has regenerated are endorgans. FIG. 5A is a schematic representation of grafting a patch ofskin 28 into the individual shown in FIG. 4 at the surgical site 30where the limb or limb portion was removed according to the embodimentof the invention of FIG. 4. FIG. 5B is a cross section of the patch ofskin 28 grafted into the individual as shown in FIG. 5A.

As represented in FIGS. 4-6D, a transfemoral amputation is again shown,but, as with the embodiment represented in FIGS. 1-3, it should beunderstood that this surgical model is applicable to any amputation withviable tissues in the amputated limb. This embodiment includes musclerelocation and recording, such as an EMG recording, as described abovewith respect to the embodiment represented in FIGS. 1-3.

This second embodiment, however, provides for cutaneous sensory input bydissecting relevant patches of skin from the amputated portion of thelimb together with the native innervation or new regenerativeinnervation, and then grafting these skin patches onto a non-anatomicalportion of the individual from whom the limb was removed. A“non-anatomical portion of an individual,” as that term is employedherein, means a tissue location that is not a natural anatomicallocation for that tissue. For example, if a foot muscle is translocatedup the leg to the thigh, it can be stated that the muscle was insertedinto a non-anatomical portion of the individual. The skin patches can betaken, for example, from a hand or foot of an individual. For a lowerextremity amputation, these skin patches would be taken, for example,from the heel, forefoot sole, and/or toe pads. One or more mechanicaldevices can then be mounted in the walls of the external prostheticsocket to provide mechanical stimulation to the grafted skin areas. Suchstimulation can be driven according to an array of appropriately locatedsensors covering the external prosthetic limb. In the case of alower-extremity prosthesis, the system can include pressure distributionnormal to the foot areas and shear forces in the anterior-posterior andmedial-lateral directions. Advanced implementation of this strategy mayalso provide information about slippage events and possibly frictionaland textural features between the ground and the shoe sole. Because thetopographic mapping of the foot skin to the brain is largely preservedfollowing the amputation, any stimulation of the transferred skin areaswill evoke tactile sensations that are referred to the foot. This samestrategy can also include relocating slips of skin from the dorsum ofthe forefoot, which can provide useful feedback for an amputee kicking asoccer ball, for example. Using synthetic external pressure and shearsensing on the prosthetic foot, a microprocessor or processors can thensend out control commands to small actuators imbedded within the socketinterface to apply equivalent pressures and shear stresses onto thecorresponding relocated skin tissues surrounding the residual limb. Forexample, when the bionic limb's heel strikes the ground surface during awalking gait cycle, small actuators imbedded within the residual socketwall may apply proportional forces to the relocated heel skin patchlocated on the residual limb surface.

In similar fashion, upper extremity amputees can benefit from feedbackof tactile events during object grasping and manipulation tasks. Asillustrated in FIGS. 6A-6D, skin patches 32 and their native innervationfrom the finger tips 34 and thumb 35 and selected locations from thepalm 36 may be relocated to the residual limb 38, where they can bemechanically stimulated by actuators 40 contained within a socket shell42 of an external prosthesis, as shown in the transition from FIG. 6C toFIG. 6D. For example, under neural control, a bionic upper extremityprosthesis can be controlled to grip the outside surface of a glass ofwater. Pressure and shear sensory information recorded within the palm36 and finger tips 34 of the prosthetic hand may be received by amicroprocessor or microprocessors located on the external prosthesis.The computer(s) can conduct computations and in turn provide controlcommands to actuators within the prosthetic socket wall 44 (See FIGS. 6Cand 6D) where commensurate pressures and shear forces may be applied tothe corresponding skin patches 32, e.g., pressure P₀ measured on theforefinger tip of the bionic hand may be applied to the forefinger skinpatch located on the residual limb surface. Such afferent feedback intothe human nervous system may then inform descending efferent motorcommands that are recorded as EMG signals from the native and relocatedmuscles, which in turn, may then be used to control the actuators withinthe external bionic hand to effectively modulate its gripping force. Theactuators within the socket wall 44 shown in FIGS. 6C and 6D that exertforces on the relocated cutaneous tissues for afferent feedback can beselected from a number of different actuator types, including but notlimited to pneumatic bladders, electroactive polymer (EAP) artificialmuscle, and electric motor with a ballscrew transmission.

Another embodiment of the present invention is to denervate a portion ofthe native skin of the residual limb during the amputation surgery, andgraft cutaneous transected nerve stumps directly to the denervated skinregion. In this framework, the cutaneous nerve axons at theresidual-limb level that once innervated skin sections of the distalamputated limb are grafted directly to the native skin in the area ofthe residual limb. By this action, skin patches need not be re-locatedfrom the distal limb, but rather the native skin of the residual limbcan be exploited for afferent feedback of force, pressure and/or shearsignals measured using synthetic sensors located on the externalprosthesis, and in turn, applied to the appropriate residual-limb skinpatch using socket actuators. It should be noted that the location ofcutaneous afferent skin patches, and the corresponding socket actuators,may be carefully selected so as not to include skin areas that arerequired to support high socket loads during afferent feedback periods.For example, the most distal aspect of the residual limb of lowerextremity amputee patients does not typically take high socket pressuresduring standing and walking, and thus such a region may be ideal forafferent feedback.

Therefore, in specific applications of this second embodiment, forexample, at least one flap of glabrous skin is dissected to therebyremove a patch of the skin from the limb, leaving intact the nativesensory innervation of the skin patch, followed by grafting the patch ofskin onto the individual at the surgical site where the limb or limbportion was removed. The grafted skin patch is contacted with anexternal prosthetic socket for the prosthetic limb. The prostheticsocket includes at least one component providing mechanical stimulationto the grafted skin. Examples of patches of skin include at least onemember selected from the group consisting of a thumb, finger, palm,heel, four foot sole, and toe pad of the individual. Preferably, thecomponent of the prosthetic socket applies pressure to a grafted patchof skin.

Third Embodiment

A third embodiment of the method of restoring at least partial functionof a human limb of the invention includes sensory feedback and, asillustrated in FIGS. 7A-7B, the use of implanted electrodes 46 atmuscles 48 and other implanted electronics 55 for registering EMGactivity. FIG. 7A is a schematic representation of contacting nativesensory innervation 50 of a skin patch 52 with nerve cuffs 54, whereinthe nerve cuffs 54 are linked to a controller 56, and selectivelystimulates native sensory innervation by actuating the nerve cuffs 54with the controller 56. Nerve cuffs 54 are linked to implantedelectronics 55 which are, in turn connected, such as by a wirelessconnection, to controller 56, as shown in FIG. 7A. FIG. 7B is anotherschematic representation of the embodiment of the invention shown inFIG. 7A, showing placement of implanted electronics and the nerve cuffsof FIG. 7A. In this embodiment, relocated distal skin 52 and its nativesensory nerves 50 are packaged inside the residual limb 58 duringamputation surgery. Sensory information is provided by electricallystimulating the sensory nerves using nerve cuffs 54 directly wrappedaround the nerves 50.

Nerve cuff technologies generally do not possess sufficient selectivityto be able to activate specific modalities of tactile afferents. Thislimits the qualities of the evoked sensory experiences to isolatedtapping events (for single pulse stimuli) or vibratory sensations iftrains of pulses are delivered. Moreover, because of these deficienciesof selectivity, known nerve cuff technologies typically do notdiscriminate well between motor and sensory fibers. Thus, nerve cuffsintended to provide sensory feedback might only be applied to puresensory nerves. For the case of mixed nerves, motor and sensoryfascicles should not be stimulated simultaneously to avoid evokingundesirable contractions in muscles innervated by the mixed nerves thatwould contribute to undesirable background signal activity, such as EMGsignal activity, in the residual limb (this complication would not ariseif following the amputation surgery, the motor fibers of a mixed nerveno longer possess connections to muscle tissue, however).

For the lower extremity, examples of targeted pure sensory nervesinclude the sural and saphenous nerves. Well-localized tactileinformation from the footsole and toes could come from cutaneousfascicles of the tibial and peroneal nerves. However, because thesenerves comprise mixed motor and sensory fibers, a neural interface thatis more selective than nerve cuffs would be required to ensure that onlythe desired sensory nerve fibers are electrically stimulated. For upperextremity applications, the distal median, ulnar, and radial nervecutaneous fascicles of the hand and fingers could be instrumented toprovide cutaneous sensory feedback.

Regarding prosthesis motor control, as was the case in embodiments ofthe invention represented in FIGS. 1-6 and associated text, muscles fromthe amputated limb are relocated with their native innervation to theresidual limb. However, whereas previous embodiments sometimes relied onsurface electrodes to record EMG signals, this third embodiment employsimplanted electrodes. More specifically, motor commands for theprosthesis can be derived from EMG signals recorded using electrodesimplanted on the epimesium of targeted muscles or using intramuscularelectrodes. It is also possible to use other EMG sensing strategies,such as mesh arrays containing electrode sites that feature embedded,distributed electronics for amplification and signal acquisition, (B.Tian, J. Liu, T. Dvir, L. Jin, J. H. Tsui, Q. Qing, Z. Suo, R. Langer,D. S. Kohane, and C. M. Lieber, “Macroporous nanowire nanoelectronicscaffolds for synthetic tissues,” Nature Materials, vol. 11, pp.986-994, 2012; and D.-H. Kim, N. Lu, R. Ghaffari, Y.-S. Kim, S. P. Lee,L. Xu, J. Wu, R.-H. Kim, J. Song, Z. Liu, J. Viventi, B. de Graff, B.Elolampi, M. Mansour, M. J. Slepian, S. Hwang, J. D. Moss, S.-M. Won, Y.Huang, B. Litt, and J. A. Rogers, “Materials for multifunctional ballooncatheters with capabilities in cardiac electrophysiological mapping andablation therapy,” Nature Materials, vol. 10, pp. 316-323, 2011).

This third embodiment also employs wirelessly powered and controlledimplanted electronics module to provide electrical stimuli to relocatedsensory nerves and to acquire EMG activity from epimesial and/orintramuscular electrodes on relocated muscles.

A similar system can be applied in cases when target skin on anamputated limb cannot be mobilized and relocated while leaving itsnative innervation intact along the entire distance from the hand orfoot sole to the residual limb. In such cases, relevant glabrous skinfrom the amputated limb is first isolated, leaving a short segment ofits native nerve attached if possible. This tissue is then implantedinto the residual limb, and a nerve-to-nerve repair is performed toconnect the individual glabrous skin samples to appropriate sensoryfascicles from amputated trunk nerves in the residual limb. The mannerof nerve repair may be end-to-end, end-to-side, or a combination ofthese. If the skin is transferred without its innervation, appropriatenerves in the residual limb are grafted directly to the transferredgrafted skin. Nerve cuffs can then be employed as previously describedto the repaired nerve for sensory stimulation.

In a closed-loop paradigm between a human and a wearable device, sensoryinformation recorded using synthetic sensors on the external deviceand/or human is mapped to appropriate afferent signals usingmicroprocessor(s) located on the wearable device. After thiscomputational step, stimulation commands are sent wirelessly to theimplanted electronics which causes electrical stimulations through thenerve cuffs. The character and magnitude of these nerve stimulationswill vary depending on the type of sensory feedback and the strength ofthat feedback. Such afferent signaling enables the human wearer tobetter modulate descending motor efferent signals that are recordedusing the implanted muscle electrodes for sensing EMG activity. Suchmuscle signals are communicated wirelessly by the implanted electronicsto the external prosthetic microprocessor(s) that then control motor(s)to drive the prosthesis.

Therefore, in this third embodiment, native sensory innervated skinpatches are contacted with the nerve cuff that is linked to a controllerand the native sensory innervation is selectively stimulated byactuating a nerve cuff with the controller. In another embodiment, thenative sensory innervation includes at least one sensory neuron selectedfrom the group consisting of sural, saphenous, tibial, peroneal, distalmedian, ulnar and radial nerves. In still another embodiment, the nervesof the transplanted selected muscles are contacted with electrodes thatare implanted on the epimesium of the selected muscles, or implantedintramuscularly in the selected muscles. In another embodiment, thetransplanted muscles are contacted with at least one mesh array thatincludes electrodes having embedded, distributed electronics thatselectively detect and amplify detected signals from the transplantedmuscles. In yet another embodiment, signals are detected from at leastone transplanted muscle and are employed to modulate signals transmittedby the controller to the native sensory innervation of the at least oneskin patch. Another embodiment further includes the step of establishinga nerve-to-nerve connection and communication between at least onesevered nerve of the transplanted skin patch and a remaining nativenerve of the individual. In another embodiment, the connection isbetween ends of the respective nerves, between the end of one nerve anda side of the other nerve, or a combination of both types ofconnections. In one specific embodiment, the electrode at thetransplanted muscle and at the nerve cuff of the grafted skin patch arelinked to the controller by a wireless connection. The connectionbetween the severed nerve of the transplanted skin patch and theremaining native nerve of the individual can be bidirectional. Yetanother embodiment further includes the step of co-locating the nerve ofthe transplanted selected muscle with the connection between the severednerve of the transplanted skin patch and the remaining native nerve ofthe individual to form a neural interface. For example, the neuralinterface can include a microchannel array having a proximal end and adistal end, wherein at least one native nerve extends from the proximalside of the microchannel array and nerves of the transplanted muscle andskin graft extend from the distal side of the microchannel array. Onespecific such embodiment further includes the step of partitioning, atthe neural interface, at least one nerve associated with thetransplanted muscle from at least one nerve associated with the skingraft. The method can further include the step of regenerating thetransplanted muscle nerve and the skin graft nerve by co-locating thetransplanted muscle nerve and the skin graft nerve with respectiveproximal native nerves at the neural interface according to theirrespective functions. In one specific such embodiment, the neuralinterface includes at least one chemotrophic substance partitioned bythe distribution of nerves within the neural interface. The neuralinterface can include at least one immunosuppressant. The method of theinvention can further include the step of mapping external sensors ofthe prosthesis to afferent signals received from at least one of thetransplanted muscles and the skin grafts, whereby the controllermodulates, at least in part, efferent signals to at least one of thetransplanted muscles and the prosthesis, to thereby at least assist theindividual in manipulating the prosthesis. Still another embodimentfurther includes the step of selectively activating nerves at the neuralinterface. Another embodiment of the method of the invention furtherincludes the step of recording signals communicated by nerves at theneural interface.

Fourth Embodiment

A fourth embodiment of the invention is a method of reversing motorimpairment of a human limb and is intended to treat the situation wheresufficient viable muscles are not available to provide adequate commandsignals, such as EMG command signals. Instead, this embodiment utilizesone or more bi-directional neural interface devices to record efferentmotor nerve activity for external prosthetic control and to allow forsensory nerve stimulation triggered by signals from artificial sensorsmounted externally on the prosthesis and/or user's body. In thisembodiment, the invention is a method of reversing motor impairment ofthe human limb including transecting a nerve associated with reducedmotor control of a limb of an individual to thereby form proximal anddistal ends of the transected nerve. The proximal and distal ends of thetransected nerve are placed in a micro channel array that includes abidirectional interface that records sensory afferent information of thenerve and that provides efferent motor stimulus to the nerve once thenerve has regenerated in the micro channel array.

In this embodiment, the method of reversing impairment of a human limbcan include transecting a nerve associated with the impairment of thelimb of an individual to thereby form proximal and distal ends of thetransected nerve. The proximal and distal ends of the transected nerveare placed into proximal and distal ends of a microchannel array,thereby causing the nerve to regenerate through the microchannel array.Sensory afferent information of the regenerated nerve is recorded usingsensing electrodes within a plurality of afferent microchannels of themicrochannel array. Motor efference information is stimulated to provideefferent motor stimulus to the nerve using stimulating electrodes withinthe plurality of efferent microchannels of the microchannel array. Thestimulating electrodes are electrically connected to a motor controllerof a device. A “device,” as that term is employed herein, can refer, forexample, to a prosthetic, orthotic or exoskeletal device. The sensingelectrodes are electrically connected a sensory controller of thedevice, wherein the sensor controller is linked to at least one sensorof the biological limb that detects application of at least one ofposition, velocity, acceleration, and force of the biological limb, andwhereby the sensory controller transmits detection of the position,velocity, acceleration, and force of the biological limb to the motorcontroller, and whereby the motor controller applies electricalstimulation via the stimulating electrodes, thereby reversingimpairments of the human limb.

In another example of the fourth embodiment, the invention is directedto a method of restoring at least partial function of the human limb ofan individual that includes dissecting at least one patch of skin fromindividual, translocating the patch of skin onto a non-anatomicalportion of the individual, wherein the skin patch includes at least onenerve selected from the group consisting of an intact native nerve and anew regenerative innervation nerve, and contacting the translocated skinpatch with an external device, the device including at least onecomponent that provides mechanical stimulation to the translocated skinpatch, thereby restoring at least partial function of the human limb.

FIG. 8A is a schematic representation of transecting nerves at targettissue 64 of a limb of an individual to thereby form distal ends 60, 61and proximal ends 63 of the transected nerve, and of placing the distalends 60, 61 and the proximal ends 63 of the transected nerves of targettissue 64 (e.g., muscle and skin) in a microchannel array 62, themicrochannel array 62 including a bidirectional interface that (1)records afferent information of the nerve and (2) provides efferentstimulus to the nerve once the nerve has regenerated in the microchannelarray, both through implanted electronics 65. FIG. 8B is arepresentation of one embodiment of placement of the microchannel arrayat the target tissue 64 of an individual and relative location of aprosthetic limb 66 controlled by the microchannel array 62. FIG. 9 is aschematic representation of the microchannel array 62 of FIGS. 8A and8B, wherein nerve fibers 68 of proximal ends 63 at an amputation sitegrow through the microchannel array 62 and connect to distal ends 60, 61arranged on the other side of the microchannel array 62. FIG. 10 is aschematic representation of another embodiment of the method of theinvention that employs microchannel array 70 wherein nerve fascicles 72from a proximal end 63 in the residual limb (not shown) are separated byfunction and placed into different channels 74 of the microchannel array70, whereby the fascicles 72 regenerate through the microchannel array70 and reconnect to the native innervation 60, 61 of appropriate targettissue 64, such as muscle and skin that have been relocated and arrangedon the other side of the microchannel array 62.

A model for amputation surgery is described here, but as will bedescribed in a subsequent section, such bi-directional neural interfacescan be implanted for the rehabilitation of spinal cord injuries, stroke,and other disabilities.

The neural interface devices (fabrication detailed in a later section)consist of an array of micro-channels with electrode contacts in eachchannel. These devices are implanted during an amputation surgery toguide nerve-to-nerve repairs between a nerve bundle proximal to theamputation site and a bundle of transected nerves from the amputatedlimb. When possible, the nerves from the amputated limb are relocatedwith their target tissues (either muscle or cutaneous) intact. Thisfourth embodiment serves the case where a nerve that subserves a targettissue that is to be relocated cannot be dissected intact along itsentire length. In that case, the nerve is transected close to its targettissue, and the tissue with its short segment of attached nerve isrelocated to the residual limb. The proximal continuation of thetransected nerve in the residual limb is then grafted to the preservedsegment of nerve attached to the target tissue. As depicted in FIG. 9,the proximal nerve in the residual limb is placed against one end of themicro-channel array, and individual nerve fibers are allowed toregenerate through the micro-channels and eventually connect to targettissues on the distal side of the array. Target tissues and theirinnervation are arranged during surgery to mirror the arrangement of therespective nerve fascicles in the proximal nerve stump, and maximize thechance that nerve fibers regenerating through channels connect to theirappropriate target tissues. In addition, as will be describedsubsequently, chemotropic substances are used to guide and sort nervefiber regeneration through the micro-channel array.

Alternatively, in cases where fascicles are largely homogenous infunction, it may be practical to employ channels with larger dimensions.In such cases, as illustrated in FIG. 10, the fascicles of the nerve inthe residual limb can be separated and individually directed intochannels of the array. The target tissue nerves are arranged on thedistal side of the array in a way that maximizes the chances of thefascicles from the residual limb (proximal nerve stump) properlyreconnecting to the correct target tissue nerves. When the nerve fibersfrom the proximal grafted nerve or grafted nerves regenerate through themicro-channels of the nerve interface, they form contacts with thechannel electrodes, which in turn are wired to an implanted electronicsmodule. As in the third embodiment, described above, this modulewirelessly communicates with a controller mounted in the shell of theprosthesis. Every channel in the neural interfaces can seamlessly switchbetween recording and stimulation as needed; a neural interface can thusbe configured as bi-directional, as desired for interfacing with a mixedproximal nerve, or the interface can be dedicated for stimulation only,as would be deployed for purely sensory nerves such as the saphenous orsural nerves of the leg. A single system can include multiplemicro-channel array devices, each of which interfaces with the proximalcontinuation of a transected nerve in the residual limb.

Prosthetic motor commands are recorded from activity that the prostheticuser generates within the efferent motor nerve fascicles of interfacednerves. Additional motor commands may be derived from recorded activityfrom surface or implanted electrodes, such as EMG electrodes, that maybe placed over muscles native to the residual limb, as would beespecially useful in the case of above-knee or above-elbow amputations.These electrodes would be wired to the same implanted electronics modulethat interfaces with all implanted micro-channel arrays. Sensoryinformation is fed back to the user by electrically activatinginterfaced sensory afferent nerve fibers using coding techniquesperformed by onboard microprocessors that recreate natural sensations asmuch as possible. This may involve stimulating nerve fibers acrossmultiple micro-channel array devices. The success of this strategydepends on the ability of an amputated peripheral nerve to regenerateinto the interface device with a high degree of selectivity by function.

Several factors have been described that influence the ability ofperipheral nerves to regenerate. Important among these is the presenceof appropriate “target tissues” or end organs for the regenerating nervefibers to reconnect with. Specifically, the axons of motor neurons needto reconnect to muscle tissue, while cutaneous sensory nerve fibers mustreconnect to cutaneous sensory end organs, such as mechanoreceptors. Thepresence of target tissues provides chemotrophic substances to which theoutgrowing neurites from a newly amputated nerve are attracted (G.Vrbova, N. Mehra, H. Shanmuganathan, N. Tyreman, M. Schachner, and T.Gordon, “Chemical communication between regenerating motor axons andSchwann cells in the growth pathway,” European Journal of Neuroscience,vol. 30, no. 3, pp. 366-375, 2009). There is evidence that the chemicalenvironment of motor nerves is slightly different from that of cutaneoussensory nerves, (G. Vrbova, N. Mehra, H. Shanmuganathan, N. Tyreman, M.Schachner, and T. Gordon, “Chemical communication between regeneratingmotor axons and Schwann cells in the growth pathway,” European Journalof Neuroscience, vol. 30, no. 3, pp. 366-375, 2009; R. Martini, M.Schachner, and T. M. Brushart, “The L2/HNK-1 carbohydrate ispreferentially expressed by previously motor axon-associated Schwanncells in reinnervated peripheral nerves,” The Journal of Neuroscience,vol. 14, no. 11, pp. 7180-7191, 1994). In particular, this is in partdue to subtle differences in the Schwann cells associated with motor andsensory axons. Because of this, it is useful to maintain a portion ofthe distal amputated nerve along with any transferred tissue that isintended to be used as a neural target tissue. Thus, the neuralinterface device, or micro-channel array, can be used as a mechanicalconnecting link or “bridge” between the proximal and distal segments ofan amputated nerve as well as an electrical connection to the nerve. Asa further exploitation of the chemotrophic effects that guide theoutgrowth of regenerating peripheral nerves, it may be beneficial to“load” or “dope” the lumen of the various micro-channels of theinterface with different chemotrophic species depending on whichspecific functional types of nerve fibers are intended to grow into thevarious micro-channels. It is also known that the mechanical andchemical features of various materials that can be loaded into the lumenof the micro-channels can influence which types of nerve fibers are mostfavored to grow into specific channels. Thus, a useful strategy tospecify which types of nerve fibers will grow into which micro-channelsof the interface is to vary the type of filler materials (that createextracellular matrices) and chemotrophic agents used in differentmicro-channels. Additionally, studies have demonstrated beneficialeffects of providing immunosuppressant drugs in enhancing both the rateand completeness of peripheral nerve regeneration across gaps causes bynerve transection (I. Sosa, O. Reyes, and D. P. Kuffler,“Immunosuppressants: Neuroprotection and promoting neurological recoveryfollowing peripheral nerve and spinal cord lesions,” ExperimentalNeurology, vol. 195, pp. 7-15, 2005).

Therefore, one embodiment of the method of the invention includescontacting the proximal and distal ends of a transected nerve with atleast one of an immunosuppressant drug, a nerve growth factor, achemotrophic drug, extracellular matrix material and neuronal supportcells.

The provision of feedback information regarding joint motion and limbposition is generally regarded as more challenging than is the case fortactile feedback. This stems mainly from the fact that (excluding directvisualization of the limb) limb motion and position sensibility isderived from several different receptor types in combination. Includedamong these is the state of stretch and relaxation of the skin thatcovers the opposing sides of the joint in question. Also, while it isknown from single afferent microneurographic recordings that the slowlyadapting cutaneous type II afferents located in the skin (at the back ofthe hand) that covers the finger joints fire in response to fingerflexion (B. B. Edin and J. H. Abbs, “Finger movement responses ofcutaneous mechanoreceptors in the dorsal skin of the human hand,”Journal of Neurophysiology, vol. 65, pp. 657-670, 1991),microstimulation of these same afferent nerve fibers individually, failsto evoke any sensory experience of skin stretch or finger motion inintact human subjects (J. Ochoa and E. Torebjork, “Sensations evoked byintraneural microstimulation of single mechanoreceptor units innervatingthe human hand,” Journal of Physiology, vol. 342, pp. 633-654, 1983). Itis hypothesized that it may be necessary to simultaneously activate anumber of such afferents in order to reach a threshold for sensoryawareness. Thus, success in employing cutaneous stretch sensitiveafferents for joint position feedback using the micro-channel interfacemay rely on being able to activate several related stretch sensitive(SAII) afferents at the same time.

In a closed-loop paradigm between a human and a wearable device, sensoryinformation recorded using synthetic sensors on the external deviceand/or human is mapped to appropriate afferent signals usingmicroprocessor(s) located on the wearable device. After thiscomputational step, stimulation commands are sent wirelessly to theimplanted electronics that causes electrical stimulations through themicro-channel array or arrays. The character and magnitude of thesenerve stimulations will vary depending on the type of sensory feedbackand the strength of that feedback. Such afferent signaling enables thehuman wearer to better modulate descending motor efferent signals thatare recorded using the electrodes within the array channels for motornerve fascicles. Alternatively, implanted muscle electrodes for sensingsignal activity, such as EMG signal activity, could be used as wasdescribed in embodiment three. Such muscle signals are communicatedwirelessly by the implanted electronics to the external prostheticmicroprocessor(s) that then control motor(s) to drive the prosthesis.

Fifth Embodiment

In a fifth embodiment of the invention, represented schematically inFIGS. 11A and 11B, the method of the third or fourth embodimentsdescribed above further includes the step of correlating recordedafferent signals from the microchannel array 80 in an algorithm togenerate motor-efferent signals at the microchannel array 80 and therebyreverse motor impairment of the human limb. In a particular embodiment,the method includes linking signals associated with the microchannelarray 80 with signals associated with a second microchannel array 82 ata second transected and regenerated nerve, and coordinating recordedsensory afferent signals and motor stimulation efferent signals of onemicrochannel array with signals of the second microchannel array, and soon for additional microchannel arrays 84, 86, 88.

Neural interfacing has become an important component of systems for therehabilitation of several disability conditions. Among these is therehabilitation of spinal injury using “Functional Electrical StimulationSystems,” or “FES.” Using various styles of cuff electrodes, forexample, developers have produced clinically useful systems that restoremotor function from otherwise paralyzed muscles by electricallyactivating the interfaced nerves. Such systems can restore graspingability to quadriplegic individuals (P. H. Peckham, B. Smith, J. R.Buckett, G. B. Thrope, J. E. Letechipia, “Functional muscle stimulationsystem,” U.S. Pat. No. 5,769,875, Jun. 23, 1998), standing and walkingto paraplegics (G. P. Forrest, T. C. Smith, R. J. Triolo, J. Gagnon, D.DiRisio, M. E. Miller, and L. Rhodi, “Use of the Case WesternReserve/Veterans Administration neuroprosthesis for exercise, standingand transfers by a paraplegic subject,” Disability and RehabilitationAssistive Technology, vol. 7, no. 4, pp. 340-344, 2012), and correctfoot-drop in individuals following stroke injury (M. Haugland and T.Sinkjaer, “Cutaneous whole nerve recordings used for correction of footdrop in hemiplegic man,” IEEE Transactions on Biomedical Engineering,vol. 3, no. 4, pp. 307-317, 1995). Aside from limb mobility, FEStechniques have also been successfully applied to provide control overother motor functions such as bowel and bladder function (G. S.Brindley, C. E. Polkey, D. N. Rushton, and L. Cardozo, “Sacral anteriorroot stimulators for bladder control in paraplegia: the first 50 cases,”Journal of Neurology, Neurosurgery, & Psychiatry, vol. 49, no. 10, pp.1104-14, 1986), and diaphragm pacing for ventilation (M. Sahin, D. M.Durand, and M. A. Haxhiu, “Chronic recordings of hypoglossal nerveactivity in a dog model of upper airway obstruction,” Journal of AppliedPhysiology, vol. 87, no. 6, pp. 2197-2206, 1999). Furthermore, theability to activate sensory nerves using an electrical neural interfacecan be applied to restoring vision in some blind populations (C.Veraart, M. C. Wanet-Defalque, B. Gerard, A. Vanlierde, and J. Delbeke,“Pattern recognition with the optic nerve visual prosthesis,” ArtificialOrgans, vol. 27, no. 11, pp. 996-1004, 2003, and providing hearingability to many otherwise deaf individuals, G. E. Loeb, “Cochlearprosthetics,” Annual Review of Neuroscience, vol. 13, pp. 357-371,1990).

With the exception of auditory neuroprostheses, rehabilitation systemsthat rely on neural interfaces have mostly provided for the activationof motor nerves. However, it is also possible to record from sensorynerves to obtain feedback information, as described in the third andfourth embodiments, that can be used in “closed-loop” control algorithmsfor restoring biological functions in disability. Some examples thathave been explored have involved sensing bladder “fullness” by recordingfrom the pudendal nerve (S. Jezernik, W. M. Grill, and T. Sinkjaer,“Detection and inhibition of hyperreflexia-like bladder contractions inthe cat by sacral nerve root recording and electrical stimulation,”Neurourology and Urodynamics, vol. 20, no. 2, pp. 215-230, 2001),sensing foot-floor contact for controlling an FES-based foot-dropneuroprosthesis (M. Haugland and T. Sinkjaer, “Cutaneous whole nerverecordings used for correction of foot drop in hemiplegic man,” IEEETransactions on Biomedical Engineering, vol. 3, no. 4, pp. 307-317,1995), and recording from the digital nerve of the thumb to sense gripforce and slippage in a grasp restoration neuroprosthesis (M. Haugland,A. Lickel, R. Riso, M. M. Adamczyk, M. Keith, I. L. Jensen, J. Haase,and T. Sinkjaer, “Restoration of lateral hand grasp using naturalsensors,” Artificial Organs, vol. 21, no. 3, pp. 250-253, 1997). All ofthese motor and sensing applications would be vastly more effective ifthe specificity of the neural interface, as well as its ability to morecompletely sample the targeted nerve, was enhanced. Optimal specificitywould allow the motor nerves innervating each individual muscle to beaddressed in isolation. With regard to sensory applications, theafferent nerve fibers that subserve each different sensory modalitywould need to be differentially addressable for stimulation and forrecording. Additionally, sensory fibers that project to different bodyregions should be accessible without undesired overlap.

In this embodiment, the method of the invention includes reversing theimpairment of an amputated limb, including inserting a distal end of atleast one transected nerve of an amputated limb into a proximal end of amicrochannel array, placing at least one member of the group consistingof skin and muscle end organ at the distal end of the microchannelarray, thereby causing the nerve to regenerate through the microchannelarray and to innervate the at least one end organ. Efferent motorinformation of the regenerated nerve is recorded using sensingelectrodes within a plurality of efferent microchannels of themicrochannel array. The regenerated nerve is stimulated with afferentsensory information using stimulating electrodes within a plurality ofafferent microchannels of the microchannel array. The sensing electrodesare electrically connected to a motor controller of a device. Thestimulating electrodes are electrically connected to a sensorycontroller of the device, wherein the motor controller is linked to atleast one sensor of the device that detects application of at least onemember selected from the group consisting of position, velocity,acceleration, and force of the device, and whereby the motor controllertransmits detection of the position, velocity, acceleration, and forceby applying electrical stimulation via the stimulating electrodes,thereby providing the individual with a sensation simulating sensoryfeedback from the device, and reversing impairment of the amputatedlimb.

The micro-channel nerve interface proposed herein is designed to achievesignificantly improved specificity for stimulation and recording ofperipheral nerve fibers, as well as exceptional long-term stability andefficacy. In the fourth embodiment, the micro-channel array wasdescribed for use in a novel limb amputation model. The fifthembodiment, depicted schematically in FIGS. 11A and 11B, describes themore generalized application of the micro-channel array for motorimpairment disabilities such as spinal cord lesion and stroke. For thefifth embodiment, a nerve 81 is transected in the affected limb that hasexperienced paralysis from a spinal cord lesion or stroke condition. Themicro-channel array is then placed between proximal 83 and distal 85nerve stumps. Through the application of factors that enhance nerveregrowth and reconnection, such as immune suppressant drugs and nervegrowth factors within the micro-channel array, the proximal nerve wouldregenerate through the micro-channel array, reconnecting to the distaltissue organs, in a nerve-to-nerve repair. Subsequent to the nerve'sfull regeneration, in a bi-directional control paradigm, sensoryafferent information from the distal biological limb, or biologicalmember, could be recorded from channels within the implantedmicrochannel arrays 80, 82, 84, 86, 88 with high specificity, and thenemployed in an artificial feedback algorithm to determine appropriatelevels of motor stimulus to be applied to distal limb muscles throughmotor channels within the same micro-channel array, or an alternatemicro-channel array attached to an alternate nerve. In the general caseof a limb that has suffered full paralysis, each major nerve of the limbcould be transected and a micro-channel array inserted for nerveregeneration. Upon regeneration through all the micro-channel arrays,mathematical mapping could be applied, linking recorded sensoryafferents from the distal limb and stimulation efferents to evoke limbmuscle activations for a whole host of stationary and movement patterns,including standing, walking and grasping. Such a mathematical mappingwould essentially replicate the dormant spinal reflexes in an artificialspinal computational framework. The artificial processor(s) to performsuch computations could be positioned external to the body, whererecorded efferents and commanded motor afferents are received andtransmitted between the computational module worn externally on thepatient (not shown) and implanted neural electronics 90.

In the next section, the micro-channel nerve interface proposed hereinfor the fourth and fifth embodiments are described.

Design and Fabrication of Micro-Channel Nerve Interface

Physical Structure—

A central element of the method of the fourth and fifth embodiments is astructure comprising an array of micro-channels that contain electrodecontacts for recording and stimulating nerve fibers. Depending on theapplication needs, some of the micro-channels may not containelectrodes. The addition of open channels (with or without electrodes)provides more places for regenerating nerve fibers to grow into. Thiscan be beneficial because it has been shown that nerve regeneration ismore robust when the “transparency factor” of the interface is greater(i.e. there is more open space vs. blockage facing the advancing edge ofthe regenerating nerve).

FIG. 12 illustrates one design configuration for fabricating athree-dimensional microchannel array 100 complete with addressableelectrode structures. The array is made from silicone (PDMS), abiologically inert material widely used in implants, and is fabricatedin a layer-by-layer process. Other materials—either natural orsynthetic—with suitable properties may also be employed. First, a˜20 μmPt/Ir foil 102 is laminated onto a thermal release tape (e.g. REVALPHA)or UV release tape 104. This foil is patterned into electrodes using aUV laser micromachining system, which has the capability to form featuresizes <100 μm. Excess foil is peeled away with tweezers. On a siliconwafer carrier 106, a micro-channel SU-8 photoresist mold 108 is createdusing standard photolithography techniques, and PDMS 112 is spun ontothis wafer to create PDMS micro-channels 110. The PDMS 112 is partiallycured at 65 C for ˜15 minutes, at which point the electrode layer isaligned and pressed into the PDMS 112. This stack is left to fully cureunder pressure at a temperature high enough to allow the thermal releasetape to lose its adhesion and be peeled away. Another thin (˜20 μm) PDMS114 layer is next spun onto the substrate to insulate the electrodes.The laser micromachining system is used to drill holes 117 in the PDMSinsulating layer 114 to the underlying metal electrodes to provideelectrical contact sites 116 within each channel. This stack, whichforms one layer of the micro-channel array 100, is then peeled away fromthe SU-8 mold 108. Multiple micro-channel layers 118 are aligned andstacked upon one another to complete the array 100. This is achieved byexposing bonding surfaces to a low-pressure (˜80 mTorr) oxygen RFplasma, which increases the density of silanol (Si—OH) groups on thePDMS surfaces. The treated surfaces are mated, allowing silanol groupsto form permanent covalent Si—O—Si bonds between the surfaces. Finally,medical-grade wires (not shown) can be laser-welded to the metalinterconnects 116 from the array for connection to an implanted controlmodule or percutaneous connector (not shown). With this process,channels with widths of ˜20 μm up to hundreds of μm can be fabricatedwith channel separations as small as ˜20 μm.

The number of micro-channels in each array and the size and geometry ofeach micro-channel are arbitrary depending on the application, and it ispossible to have different sized channels intermixed with each other.Larger channels would allow greater numbers of nerve fibers to grow intothem, enabling the sampling of a greater number of nerve fibers toprovide a higher amplitude signal (if the fibers were activatedconcomitantly). A narrow channel could increase the specificity of thenerve recordings by reducing the number of sampled fibers.

FIG. 13A is an exploded view of one embodiment of a three-dimensionalmicrochannel array 120 suitable for use by at least one method of theinvention. Shown are channels 122 and interconnects 124. FIG. 13B is aperspective view of the assembled three-dimensional microchannel array120 of FIG. 13A.

Other Design Considerations of the Novel Peripheral Nerve Interface:

Modularity—

An advantage of the micro-channel design is that the physical dimensionsof the implant device can be customized depending on the size andfascicular structure of the targeted nerve or nerves. This can be donesimply by changing the mask used during photolithography or by combiningtwo or more smaller arrays.

Use of Target Tissues—

The novel design of the nerve interface makes use of “target tissues”which assists the regenerating proximal sensory and motor nerve fibersto re-connect with their appropriate end organs harvested from thedistal limb. This assures that the regenerated nerve will be stable overthe long term so that a neural-based control system does not have to be“tuned” or modified often.

Moreover, the incidence of neuroma formation is substantially reducedwhen the outgrowing nerve fibers from a transected peripheral nerve areconstrained and are able to reconnect with their preferred targettissues, (J. T. Aitken, “The effect of peripheral connexions on thematuration of regenerating nerve fibres”, Journal of Anatomy, vol. 83,no. 1, pp. 32-43, 1949); A. L. Dellon and S. E. Mackinnon, “Treatment ofthe painful neuroma by neuroma resection and muscle implantation,”Plastic and Reconstructive Surgery, vol. 77, no. 3, pp. 427-38, 1986;and T. Okuda, O. Ishida, Y. Fujimoto, N. Tanaka, A. Inoue, Y. Nakata,and M. Ochi, “The autotomy relief effect of a silicone tube covering theproximal nerve stump,” Journal of Orthopaedic Research, vol. 24, number7, pp. 1427-37, 2006). An important benefit of this is that thepossibility for the development of phantom limb pain is thensubstantially lowered as well (H. Cravioto and A. Battista, “Clinicaland ultrastructural study of painful neuroma,” Neurosurgery, vol. 8, no.2, pp. 181-90, 1981).

Use of Chemotropic Agents—

Chemo-attractants may be added to the interface device to direct theregrowth of different types of nerve fibers differentially. It ispossible to add extracellular matrix materials as well as neurotrophicsubstances to specific micro-channels in an effort to achieve separationamong the various types of regenerating motor and sensory nerve fibers.These efforts may also include the use of neuronal support cells, suchas Schwann cells, that are specific for different types of nerve fibers(G. Vrbova, N. Mehra, H. Shanmuganathan, N. Tyreman, M. Schachner, andT. Gordon, “Chemical communication between regenerating motor axons andSchwann cells in the growth pathway,” European Journal of Neuroscience,vol. 30, no. 3, pp. 366-375, 2009; and R. Martini, M. Schachner, and T.M. Brushart, “The L2/HNK-1 carbohydrate is preferentially expressed bypreviously motor axon-associated Schwann cells in reinnervatedperipheral nerves,” The Journal of Neuroscience, vol. 14, no. 11, pp.7180-7191, 1994).

Sixth Embodiment

In a sixth embodiment, the invention is directed to a method forsimulating a proprioceptive sensory organ for a limb or organ, andincludes mechanically linking at least one pair of agonist andantagonist muscles. In one embodiment, at least one of the muscles of atleast a portion of the pairs of agonist and antagonist muscles includesat least one member selected from the group consisting of a Golgi tendonorgan, muscle spindle stretch fibers, and an efferent/afferent nerve. Inone specific embodiment, the Golgi tendon organ, the muscle spindlestretch fiber or afferent/efferent nerve is preserved intact. At leastone pair of agonist and antagonist muscles are supported, wherebycontraction of the a muscle of each pair causes extension of the pairedmuscle. In one embodiment, the Golgi tendon organ of the agonist muscleand the spindle stretch fibers of the antagonist muscle will generateafferent signals. An electrode, such as an electromyographic electrode,is implanted in each of the agonist and antagonist muscles of each pair.In one embodiment, the electrode senses and stimulates musclecontraction. The electrodes are electrically connected to a motorcontroller of a device. In one embodiment, the device includes at leastone member selected from the group consisting of a prosthesis, orthosisor exoskeleton. In one embodiment, a position about a degree of freedomof the device can be sensed by an individual wearing the device, theagonist and antagonist muscles, thereby simulating a proprioceptivesensory organ for a human limb or organ.

This embodiment describes novel Regenerative Peripheral Nerve Interface(RPNI) models for providing 1) efferent motor agonist/antagonist signalsfor the control of external prosthetic motors, and 2) proprioception andcutaneous afferent feedback into peripheral nerves from externalprosthetic sensory signals. The proposed models are unique in theirpotential capacity to utilize native tissue mechanoreceptors totranslate prosthetic sensory information related to muscle stretch andtension, as well as skin pressure and shear, into neural signals similarto those experienced in the normal biological milieu. In contrast toalternative approaches to afferent feedback that bypass nativebiological tissues, the proposed models incorporate the specializedbiomechanical structures inherently present in muscle and skin totransduce information regarding muscle fascicle state and force, as wellas skin mechanoreceptor strain. In utilizing biological structures inthe design of these systems, when integrated with currentstate-of-the-art bionic limb prostheses, amputees are expected toexperience proprioceptive and cutaneous sensory feedback thatapproximates or equals that of their previously uninjured state whilesimultaneously providing a safe and viable peripheral neural interface.

These designs extend the functionality of traditional RPNIs, aspreviously described by the seminal work of Cederna et al. (M. G.Urbanchek, J. D. Moon, K. B. Sugg, N. B. Langhals, P. S. Cederna, Z.Baghmanli, “Regenerative peripheral nerve interface function at 1 and 3months after implantation,” Plastic & Reconstructive Surgery, vol. 130,no. 1S, pp. 84, 2012). A traditional RPNI is a surgical construct inwhich a segment of nonvascularized muscle is approximated with thedistal terminus of a peripheral nerve and is subsequently reinnervatedto provide a stable biological substrate for neural interaction. Todate, RPNIs have been described primarily as a means to achieve efferentmotor signals from a single muscle construct constrained to onlygenerate isometric force; when innervated by a peripheral motor nerve,the isometric muscle unit serves as an amplifier of neural activationthat may be recorded using standard EMG electrodes and used for thecontrol of synthetic actuators in an external prosthesis (C. M. Frost,D. C. Ursu, A. Nedic, C. A. Hassett, J. D. Moon, S. L. Woo, R. B.Gillespie, P. S. Cederna, N. B. Langhals, M. G. Urbanchek,“Neuroprosthetic hand real-time proportional control by rodentregenerative peripheral nerve interfaces,” Plastic & ReconstructiveSurgery, vol. 133, no. 4S, pp. 1012-3, 2014). However, since the muscleis held isometrically, realistic muscle fascicle strains cannot beachieved. Further, an antagonist muscle is not stretched when theinnervated agonist contracts, eliminating realistic spindle fiberfeed-back from the antagonist when an external prosthetic joint flexes.Finally, current motor RPNI technology does not allow the force on theinnervated muscle construct to be modulated by an antagonist muscle soas to allow force feedback from an external prosthesis.

More recently, sensory RPNIs have been demonstrated (J. V. Larson, M. G.Urbanchek, J. D. Moon, D. A. Hunter, P. Newton, P. J. Johnson, M. D.Wood, T. A. Kung, P. S. Cederna, and N. B. Langhals, “Prototype sensoryregenerative peripheral nerve interface for artificial limbsomatosensory feedback,” Plastic & Reconstructive Surgery, vol. 133, no.3S, pp. 26-27, 2014). Here, afferent signaling in principle can beachieved by having a sensory nerve innervate an isometric musclecomponent, and then artificially stimulating that innervated muscle tomodulate the afferent signal. Although a critically important stepforward for the field, such an RPNI design does not incorporate nativeskin mechanoreceptors for realistic skin strain feedback. Further, thedesign has not been tested in human subjects to provide a means ofassessing how such non-specific afferent signaling from contractingisometric muscle fibers would be perceived.

Proprioceptive Muscle RPNI (Pro-m-RPNI)

The fundamental motor unit to control a biological joint is anagonist-antagonist muscle-tendon pair. Such a muscle-tendon relationshipallows organisms to simultaneously control joint state (position andspeed) and impedance (stiffness and damping) for upper and lowerextremity motor tasks. At least one pair of antagonistic muscles areneeded for each degree of freedom of a limb in order to control bothjoint state, torque and impedance. Although only one Pro-m-RPNI isdescribed per prosthetic degree of freedom, it should be understood bythose of ordinary skill in the art that a plurality of Pro-m-RPNIdevices could be employed in the control of each degree of freedom of aprosthetic, orthotic or exoskeletal limb.

A major input to joint state afferent sensory information derives fromthe muscle spindle receptors which are known to discharge when a muscleis passively elongated, but which stop firing abruptly whenever thatmuscle is slackened passively (R. R. Riso, F. K. Mosallaie, W. Jensen,and T. Sinkj er, “Nerve cuff recordings of muscle afferent activity fromtibial and peroneal nerves in rabbit during passive ankle motion,” IEEETransactions on Rehabilitation Engineering, vol. 8, no. 2, pp. 244-258,2000). When a muscle undergoes an active contraction, however, thedischarges from spindle receptors within that muscle could halt or bemodified, depending on any activation of spindle intrafusal musclefibers via Gamma motor neurons (M. Hulliger, “The mammalian musclespindle and its central control,” Reviews of Physiology, Biochemistryand Pharmacology, vol. 101, pp. 1-110, 1984).

In yet another embodiment of the invention, the method includessimulating proprioceptive sensory feedback from a device, including thesteps of the mechanically linking at least one pair of agonist andantagonist muscles, wherein a nerve innervates each muscle. The at leastone pair of agonist and antagonist muscles are supported with a support,whereby contraction of the agonist muscle of each pair will causeextension of the paired antagonist muscle. At least one electrode isimplanted in at least one muscle of each pair, and the at least oneelectrode is electrically connected to a motor controller of the device,thereby stimulating proprioceptive sensory feedback from the device.

FIG. 14 depicts the coupling of an agonist-antagonist muscle pair usinga flexible “I-beam joint” structure 130. As illustrated in FIG. 14, whena muscle 132 on one side of a I-beam joint structure contracts (e.g.,muscle A) and moves the joint 130, this motion elongates the muscle 134that is attached to the opposite side of the joint 130 (e.g., muscle B)and causes the muscle 134 spindle receptors to discharge. Similarly, ifcontraction of muscle 134 causes the joint 130 to rotate towards theopposite direction, then muscle 132 will be elongated causing the muscle132 spindle receptors to discharge. Presumably, the arithmeticdifference between the activity levels of muscle 132 and muscle 134spindle afferents would be representative of the “joint” 130 position.This thesis is supported by studies in which the flexor and extensortendons of the biceps and triceps muscles in the fixated arm of normalhuman subjects were vibrated individually or the flexor and extensortendons were vibrated simultaneously (J. P. Roll and J. P. Vedel,“Kinesthetic role of muscle afferents in man, studied by tendonvibration and microneurography,” Experimental Brain Research, vol. 47,no. 2, pp. 177-190, 1982), (the vibratory stimulus causes the spindlereceptors in the vibrated muscle to discharge). When the biceps tendonwas vibrated alone, subjects reported a sensation that the elbow wasextending, whereas if the triceps tendon was vibrated alone the subjectsperceived that their elbow was moving in the flexion direction. Fastervibration resulted in a higher perceived velocity of the limb motion.Finally, if the biceps and triceps tendons were vibrated at the sametime and using the same frequency, then the elbow position was perceivedto remain stationary. However, if the frequency of vibration wasdifferent for the biceps and triceps during the simultaneous vibrationstudies, then the perception of limb movement was toward flexion whenthe triceps was driven at the faster frequency and the motion wasperceived toward extension if the biceps received the faster vibratorystimulation.

This “push-pull” system that exists on each side of a joint in normalphysiology can be mimicked when transferring muscles by placing them inopposition to each other using some kind of mechanical system thatcouples their movements to each other. One mechanical design that couldaccomplish this coupling is the compliant I-beam device shown in FIG.14. Such a mechanical structure could be fabricated from variousmaterials having arbitrary stiffness profiles at the points of muscleattachments and for the deformable beam that connects to the pair oftethered muscles.

To achieve an agonist-antagonist interaction, other muscle-tendonconfigurations are possible. Alternative configurations to theaforementioned I-beam structure are the Pro-m-RPNIs shown in FIG. 15-17.These configurations incorporate motor RPNIs from discreteagonist-antagonist muscle pairs (e.g. ECRB and FCR) attached in series.In one case, shown in FIG. 15, the muscles 143 and 145 of muscle pair140, with their native Golgi tendon organs 142 and intrafusal musclespindle stretch fibers 144, are sutured or bonded togethertendon-to-tendon at one end 146 to form a series combination. The twofree ends 148, 150 of the linearly-coupled, muscle-tendon arrangementare then secured to a biological or synthetic structure. Ideally, thelinear RPNI is simply secured to bone 152 to avoid the difficulty ofmaking a biological-to-synthetic interface. When a synthetic materialmust be used, as illustrated in FIG. 16, the structure may be made of astiff material 154, such as titanium, or a more compliant one, such assilicone, as desired. Depending on the material of the structure, asmall piece of the bone at the native tendon-bone attachment site may bepreserved to enable the attachment of the muscle-tendon piece to thestructure. FIG. 17 is a representation of a Pro-m-RPNI schematic about asynthetic spool shown comprising: 1) a synthetic spool; 2) an agonistmuscle; 3) an agonist motor/afferent nerve; 4) an agonist electrode forelectromyographic sensing and functional electrical stimulation; 5)agonist muscle spindle fibers; 6) an agonist Golgi tendon organ; 7) anantagonist muscle; 8) an antagonist motor/afferent nerve; and 9) anantagonist electrode for electromyographic sensing and functionalelectrical stimulation. As shown in FIG. 17, Pro-m-RPNI muscle pair 155is secured into a loop around a low-friction synthetic spool 158.Contraction of the agonist muscles 143,156 via the standard motor nerves141,157 efferent of one muscle will provide electrode signaling, such asEMG signaling, by the antagonist muscles 145,159 to an externalprosthetic actuator through electrodes 147,161 as in a standard motorRPNI; however, it will simultaneously activate the native contractilemechanoreceptors in the Golgi tendon organs 142,163 of the agonistmuscles 143,156, as well as the native intrafusal muscle spindle stretchfibers of the mechanically-coupled antagonist muscles 145,159, both ofwhich will provide afferent proprioceptive signaling through the sensorycomponents of their respective innervation nerves. Subsequent volitionalactivation of the antagonist muscles 145,159 will stimulate acomplimentary stretch on the agonist muscles 143,156; as such, thisproprioceptive RPNI will demonstrate a more realistic agonist-antagonistmechanical coupling providing non-isometric fascicle strains andagonist-antagonist fascicle state spindle feedbacks.

While this strategy may seem simple conceptually, because muscle spindlereceptors exist in several different varieties with each having slightlydifferent response properties (A. B. Vallbo, “Basic patterns of musclespindle discharges in man,” in Muscle Receptors and Movement, A. Taylorand A. Prochazka, Eds. London: Macmillan, 1981, pp. 263-275), it wouldbe best if the innervation to a selected pair of agonist and antagonistmuscles is able to be left intact to those muscles so that the brain caninterpret the spindle discharge information with minimal retraining. Incases where the translocated muscle requires that its innervation bereplaced by nerve repair (where some misconnection of some afferentfibers to end organs may occur), practical experience with implantedamputee subjects will determine if mechanisms of cortical plasticity areable to interpret the sensory afferent activity from the reconnectedspindle and tendon receptors sufficiently to provide satisfactoryinformation regarding joint motion, position and force.

Furthermore, the Pro-m-RPNI framework will also allow force feedbackfrom Golgi tendon organs within the agonist and/or antagonist. When theagonist contracts, for example, the level of antagonist activation orco-contraction, will determine the force borne by the agonist, and sucha force will be communicated as an afferent signal through the sensorycomponents of its respective innervation nerve.

For the Pro-m-RPNI, electrodes are placed over each muscle of theagonist-antagonist pair. Such electrodes can be used for motor intentacquisition by recording muscle electromyography (EMG) for use as aprosthetic control signal. The level of common mode muscle activation,or co-contraction, measured by the EMG electrodes on theagonist-antagonist muscle pair, can be used to determine the user'sintent for prosthetic joint impedance (stiffness and damping). Indistinction, the differential in measured EMG signals can be employed todetermine joint state (position/speed).

In addition, such electrodes can apply functional electrical stimulation(FES) for prosthetic force feedback from an external prosthesis; byapplying FES on the antagonist as the agonist contracts, the force onthe agonist can be controlled by the external prosthetic processorsbased upon synthetic force sensory information from the correspondingprosthetic joint. For example, when an upper extremity prosthetic userpicks up a bar bell weight and flexes her prosthetic wrist, thePro-m-RPNI corresponding to wrist flexors/extensors can be electricallystimulated so the user can experience the bar bell weight; as thePro-m-RPNI agonist muscle contracts, with a motor nerve supply that onceinnervated the wrist flexors prior to limb amputation, an FES controlcan be applied to the Pro-m-RPNI antagonist muscle, increasing the forceborne by the agonist. The magnitude of the FES stimulation signal wouldbe proportional to the estimated force that would have been applied bythe wrist flexors against the bar bell load prior to limb amputation.

The Pro-m-RPNI structures of FIGS. 15-17 can also employ fascicleposition and speed sensors. For example, sonomicrometer crystals can bestitched into muscle fibers (J. A. Hoffer, A. A. Caputi, I. E. Pose, R.I. Griffiths, Prog. Brain Res. 80, 75 (1989)). Sonomicrometry has beenused successfully to measure skeletal muscle length changes in situ andduring walking in cats, J. A. Hoffer, A. A. Caputi, I. E. Pose, R. I.Griffiths, Prog. Brain Res. 80, 75 (1989), and running in turkeys, T. J.Roberts, R. L. Marsh, P. G. Weyand, C. R. Taylor, “Muscular force inrunning turkeys: the economy of minimizing work,” Science, 275 (5303),1997, 1113-1115. Sonomicrometry is a technique of measuring the distancebetween piezoelectric crystals based on the speed of acoustic signalsthrough the medium for which they are embedded, the medium for thisinvention being muscle tissue. Typically, the crystals are coated withan epoxy and placed into the muscle facing each other. An electricalsignal sent to either crystal will be transformed into sound, whichpasses through the tissue, eventually reaching the other crystal, whichconverts the sound into an electric signal, detected by a receiver. Fromthe time taken for sound to move between the crystals and the speed ofsound through tissue, the distance between the crystals can becalculated, or the displacement of a muscle fiber.

When the fiber contracts or is stretched, the relative position of thecrystals can thus be measured, and the fiber length determined. Such ameasurement of fascicle state can be used in the bi-directional controlof a bionic limb. Pro-m-RPNI measured state information can be used tocontrol bionic joint state; as the agonist contracts and the antagonistis stretched, or vice versa, the agonist/antagonist lengths and speedscan be used as control targets by the external bionic limb controller tooutput corresponding bionic limb joint positions and speeds. However, toaccurately estimate joint state, both the length of the muscle fibersand the tendon length must be determined. Tendon length can be estimatedfrom the force applied on the tendon and its stiffness. To determinemuscle-tendon force, a muscle model (e.g. Hill muscle model) can beused. Running on the micro-computers on the external bionic limb, amuscle model can estimate the forces borne by the Pro-m-RPNIagonist/antagonist muscles using sensory inputs of muscle EMG levels andfascicle positions and speeds. Alternatively, to attain muscle forcesensory information from the Pro-m-RPNI muscles, a force sensor can beimplanted as part of the Pro-m-RPNI device. For example, strain gaugesensors 149 can be applied near the tendon-bone interface, shown in FIG.15, of the various Pro-m-RPNI configurations. Strain gauges (e.g. TokyoSokki Kenkyujo Ltd.) can be glued to the internal and external aspectsof the free calcified tendon with the use of methods developed for bone(A. A. Biewener, Biomechanics: Structures and Systems (Oxford Univ.Press, Oxford, (1992)). Also, force buckles can provide measurements offorces in individual muscles (B. Walmsley, J. A. Hodgson, R. E. Burke,J. Neurophysiol. 41, 1203 (1978)), and could be employed for this neuralinterface device.

Alternatively, FES control applied by the external bionic limbcontroller can exert a position control on the agonist/antagonistmuscles of the Pro-m-RPNI by closing the loop using the measuredfascicle states. In the case where an external agent is positioning theexternal bionic joint, such positions would have to be reflected on theagonist/antagonist muscles in order for the prosthetic user to receiveaccurate proprioceptive feedback. For example, if another person graspsthe bionic hand of the prosthetic user with their hand in order to shakethe hand of the prosthetic user, such a handshake may forcibly changethe positions of the bionic joints. Bionic joint state sensoryinformation would serve as control position and speed targets for a FEScontrol applied to the Pro-m-RPNI muscles by microprocessors positionedon the bionic limb. For example, if the handshake flexed the bionicwrist, the FES controller would receive bionic wrist state informationfrom a synthetic wrist sensor, and apply an electrical activation to theagonist Pro-m-RPNI muscle proportional to the error between the measuredbionic wrist position/speed and the measured position/speed from musclefiber state sensors, causing the muscle to contract and the antagonistto stretch. The prosthetic user would then experience the position oftheir bionic wrist as imposed by the handshake through an afferentfeedback to the spinal cord from muscle spindle receptors in theagonist/antagonist pair.

Therefore, the methods of the invention for simulating a proprioceptivesensory organ for a human limb or organ can variously include thefollowing specific embodiments. In one embodiment, the method includesthe step of mechanically linking a plurality of pairs of agonist andantagonist muscles to at least one degree of freedom of the prosthesis,orthosis or exoskeleton. In another embodiment, the method furtherincludes the step of associating a plurality of pairs ofelectromyographic electrodes, each pair of electromyographic electrodesbeing electrically connected to a pair of agonist and antagonistmuscles, with a plurality of degrees of freedom of the prosthesisorthosis or exoskeleton, each degree of freedom of the prosthesis,orthosis or exoskeleton being associated with at least one pair ofelectromyographic electrodes of an agonist/antagonist muscle pair. Inyet another embodiment, at least one pair of the linkedagonist/antagonist muscles is supported by a biological structure, suchas a human bone. Alternatively, or additionally, at least one pair ofthe linked antagonist/antagonist muscles is supported by an artificialsupport. In a specific embodiment, the agonist/antagonist muscles of thepair are linked linearly to each other at one end, and linked at theirrespective free ends to the artificial support. At least one of therespective free ends of the agonist/antagonist muscle pair includesnative bone, which bone can be secured to the artificial support. Inanother embodiment, the agonist/antagonist muscles of the pair arelinked to each other by the artificial support. In one embodiment, theartificial support is a lever, in which one end of each muscle isattached to an arm, the arms being on opposite sides of a fulcrum of thelever, whereby contraction of one muscle of the agonist/antagonist paircauses extension of the other muscle of the agonist/antagonist pair. Inanother embodiment, the ends of each agonist/antagonist muscle pair arelinked to each other to form a closed loop, and the muscle extends abouta periphery of the artificial support, whereby contraction of one of themuscles of the pair will cause extension of the other muscle of thepair. A particular method of the invention further includes the step ofimplanting in at least one agonist/antagonist muscle pair at least onemember of the group consisting of a force sensor and a position sensor.The position sensor can include, for example, a plurality ofpiezoelectric crystals, such as sonomicrometer crystals. In a specificembodiment of the method of the invention, the relative positions of theimplanted crystals are employed to establish a control target of speedand length of the agonist/antagonist muscle pair by the controller tothereby estimate the joint state of the prosthesis, orthosis orexoskeleton. Estimating the joint state can further include the steps ofmeasuring the force applied and the stiffness of a tendon component ofat least one of the muscles of the agonist/antagonist muscle pair, andcombining those measurements with the measurements of speed and lengthof the corresponding muscles of the muscle pair wherein the force sensorincludes at least one of a strain gauge and a force buckle. A motorcontroller 182 (see, e.g., FIG. 20 and accompanying description) canemploy the strength of an electromyographic sensory signal measured atthe agonist/antagonist muscle pairs, and position and speed of theagonist/antagonist muscle pairs to estimate joint state. In anotherembodiment, the motor controller can detect motion in the prosthesis,orthosis or exoskeleton, and relay that information by selectivelystimulating at least one muscle of the agonist/antagonist pair, therebycausing the individual wearing the prosthesis, orthosis or exoskeletonto sense the change in position of the prosthesis, orthosis orexoskeleton.

Cutaneous RPNIs

In yet another embodiment, the invention is directed to simulating acutaneous sensory organ for a human limb or organ of an individual byexcising a skin segment from a limb or portion of a limb, the skinsegment including innervating nerve. The skin segment is linked to atleast one muscle having a nerve supply, and an electrode is implanted inat least one muscle. The skin segment and actuator muscle are supportedon a support. The electrodes are electrically connected to a sensorycontroller of a device, such as prosthesis, orthosis or exoskeleton, andthe controller is linked to a sensor of the device. The controllerdetects application of at least one member selected from the groupconsisting of stress, strain, contact, pressure and sheer at the device,and transmits detection of the stress, strain, contact, pressure orsheer by contracting the actuator muscle with the electrode, therebystretching the mechanoreceptor of the skin segment and providing theindividual with a sensation simulating cutaneous sensation at the limb.

In a specific embodiment, at least one pair of agonist and antagonistmuscles are mechanically linked, and wherein a nerve innervates eachmuscle. In one embodiment, at least one muscle of at least a portion ofthe muscle pairs includes at least one member selected from the groupconsisting of a Golgi tendon organ, muscle spindle stretch fibers, andan efferent/afferent nerve. At least one pair of agonist and antagonistmuscles are supported, whereby contraction of a muscle of each pair willcause extension of the paired muscle. In one embodiment, the Golgitendon organ of the agonist muscle and the muscle spindle fibers of theantagonist muscle will generate afferent signals. An electrode isimplanted in each of the agonist and antagonist muscles of each pair. Inone embodiment, each electrode senses and stimulates muscle contraction.The electrodes are electrically connected to a motor controller of adevice. In one embodiment, the device includes at least one memberselected from the group consisting of a prosthesis, an orthosis and anexoskeleton. In one embodiment, a position about a degree of freedom ofthe prosthetic, orthotic or exoskeleton can be sensed by an individualwearing the prosthesis, orthosis or exoskeleton, thereby functioning asan artificial proprioceptive sensory organ for a human limb or organ.

In one embodiment, the invention is a method for simulating cutaneoussensory feedback from the device, including steps of excising a skinsegment from a biological body part of an individual, the skin segmentincluding at least one of a native nerve and a regenerative nervesupply. The skin segment is linked to at least one muscle having a nervesupply. An electrode is implanted in the at least one muscle. The skinsegment and actuator muscle are supported on a support. The at least oneelectrode is electrically connected to a sensory controller of a device,wherein the controller is linked to a sensor of the device that detectsapplication of at least one of stress, strain, contact, pressure andsheer at the device, and whereby the controller transmits detection ofthe stress, strain, contact, pressure or sheer by contracting theactuator muscle within electrical stimulation via the electrode, therebystretching the mechanoreceptor of the skin segment and providing theindividual with a sensation stimulating cutaneous sensory feedback fromthe device.

As can be seen in FIG. 18, Cutaneous Sensory RPNIs (Cut-s-RPNI) 160 maybe assembled in a similar manner to the previously described Pro-m-RPNIsto achieve controllable skin strain feedback signals from implantedbiological skin mechanoreceptors. Specifically, Cut-s-RPNIs can beconstructed so as to incorporate a motor RPNI 162 in series with aninnervated strip of de-epithelialized skin 166 around a central, lowfriction synthetic spool 164. In this embodiment, the de-epithelializedskin is a strip of skin 166, and is attached to the actuator muscle atopposite ends of the strip. The artificial support is a spool 164 andthe de-epithelialized skin 166 and actuator muscle are supported aboutthe periphery of the spool 164. To achieve multi-directional skin strainfeedback, Cut-s-RPNIs may also be constructed by attaching a skin patch168 to multiple motor RPNIs 170,172 around a low friction syntheticsphere 174, as shown in FIG. 19. In this embodiment, the artificialsupport is spherical and the de-epithelialized skin is linked to twoactuator muscles that, when contracted, provide tension to thede-epithelized skin in different directions, each actuator muscle beingimplanted with a separate electromyographic electrodes 171,173respectively controlled independently by the controller (not shown).Measurements of orthogonal strain (pressure) and tensile shear strainfrom prosthetic limb sensors will determine FES control commandsresulting in contraction of the muscle via electrode signaling, whichwill, in turn, produce proportional stretch and pressure across theinnervated skin strip. Activation of native mechanoreceptors in the skinstrip will provide cutaneous sensory feedback through the sensory nerve175 associated with the skin strip via standard afferent pathways. Itwill be understood by those of ordinary skill in the art that the spooland sphere structures shown in FIG. 18 can be modified to includenon-circular cross sections such as oval cross sections (not shown). Theexact shape of these structures can be varied to adjust the relationshipbetween skin pressure and tensile stretch when the muscle(s)contract(s). Similar to the Pro-m-RPNI device described earlier, themuscle(s) of the Cut-s-RPNI can employ implanted sensors that directlymeasure its fascicle states and forces. As stated earlier,Sonomicrometry can be used to measure fiber length and speed, and straingauges or force buckles can be used to measure muscle-tendon force.Processors on the external bionic limb can then apply a closed loopcontrol on the skin patch of the Cut-s-RPNI so as to apply controlledskin strains, pressures and shear forces reflecting measured target skinstrains, pressures and shear forces recorded by the external prostheticsensors.

Control integration of the Pro-m-RPNI 176 and Cut-s-RPNI 178 deviceswith an external bionic prosthesis 180 is illustrated in FIG. 20. Inthis embodiment, the method further includes motor controller 182 thatuses a biomechanical model of the missing limb to map the state(fascicle length and speed) and EMG of the agonist/antagonist muscleswithin the Pro-m-RPNI 176 into a corresponding joint state (angle andangular rate) and joint torque/impedance of the associated degree offreedom within the bionic prosthesis 180. The motor controller 182 thenapplies a feedback control using the biomimetic joint state andtorque/impedance as control targets. Further, motor controller 182 alsofeedbacks force by measuring torque at the associated bionic prosthesis180 degree of freedom, mapping that torque to correspondingmuscle-tendon forces, and then applying a functional electricalstimulation (FES) control on the muscle that applies a joint torque inthe same direction as the measured applied torque thereby modulating theforce on the muscle oriented to counter the measured torque. Forexample, for a measured extension torque at a bionic limb degree offreedom, a FES control is applied on the muscle that is associated withjoint extension, thereby modulating the force borne by the opposingmuscle that is associated with joint flexion, providing the prostheticuser a direct force feedback from the bionic limb via Golgi tendon organsensing.

FIG. 20, also depicts a sensory controller 184. This controller mapsmeasured force and shear from the prosthetic sensors into FES signals onthe muscle, or muscles, that exert forces on the skin patch of theCut-s-RPNI. The sensory controller 184 modulates the FES signal untilthe fascicle state of the Cut-s-RPNI muscle, and corresponding skinforce/shear on the Cut-s-RPNI skin patch, are achieved based upon thetarget force/shear measured from the external prosthesis 180. Throughthe sensory controller 184, a realistic cutaneous feedback is achievedfrom the bionic prosthesis 180.

The specific example of a prosthetic user reaching for a bar bell,grasping the bar bell, and then doing a wrist curl is provided toexplain the efferent/afferent bi-directional control of the bionic limb180 described in FIG. 20. The prosthetic user sees the bar bell anddecided to reach and grasp it. Upon reaching, descending efferent motorcommands activate the agonist and antagonist muscles of the Pro-m-RPNI176 corresponding the wrist flexors/extensors. For purposes of thisexample, only the bionic wrist is described, but it should be understoodthat each degree of freedom of the bionic limb would be controlled by atleast one Pro-m-RPNI. A plurality of Pro-m-RPNI devices could be used tocontrol a single degree of freedom if a modulated joint impedancecontrol were sought. Similar to the human body where often multipleagonist-antagonist pairs span a single joint, so too multiplePro-m-RPNI's can be employed to control a single bionic degree offreedom.

The respective nerve supply for the agonist and antagonist transmitproprioceptive information as an afferent signal to the user's spinalcord. Golgi tendon organs transmit forces while spindle fibers transmitspeeds and displacements allowing the prosthetic user to feel theirsynthetic wrist stiffen and position itself for proper orientation tograsp and manipulate the bar bell.

Further, agonist/antagonist Pro-m-RPNI muscle activations and fasciclestates are recorded via electrodes and fiber sonomicrometer crystals,respectively, and sent wirelessly to processing modules located on thebionic limb referred to in FIG. 20 as the motor controller 182. Suchsignals might also be transmitted directly through wires passing throughan osseo-implant to the external bionic limb. A biomimetic model of themissing human limb is then used by the bionic limb controller to mapPro-m-RPNI agonist/antagonist muscle state and EMG levels tocorresponding muscle forces using a skeletal muscle model such as theHill model. In an alternate embodiment, an implanted force sensordirectly measures agonist/antagonist force levels, and that sensoryinformation is communicated to the external bionic limb microprocessors.Once the modeled muscle-tendon forces and states are estimated, thebiomimetic limb model is then used to map these muscle forces and statesto the resulting wrist torque, impedance and joint state of theprosthetic wrist, by conducting a geometric transformation using jointmoment arm and joint position information. The biomimetic limb modelcomputes control targets for the bionic limb wrist controller withtarget wrist torque, impedance and joint state. A closed-loop controllerrunning on the motor controller 182 then servos to such targets. Thus,through neural control, the prosthetic user can control the prostheticwrist's position, torque and impedance while feeling the movement of theprosthetic wrist through afferent signaling from spindle fibers withinthe agonist/antagonist Pro-m-RPNI.

Through FES on the Pro-m-RPNI 176 muscles, force and state sensoryinformation can be transmitted into the nervous system. For example,once the bionic hand grasps the bar bell (via control from fingerPro-m-RPNIs), the user contracts the agonist (corresponding to wristflexor), stretching the antagonist, and providing the sensation of wristmovement. As load from the bar bell is applied to the bionic limb, theantagonist muscle can be activated with a FES control, increasing theforce exerted on the contracting agonist muscle proportional to theestimated force exerted by the modeled wrist flexors of the biomimeticmodel necessary to achieve the measured wrist joint torque levels.Through this force feedback, the prosthetic user can feel the weight ofthe bar bell as it is being lifted throughout the wrist curl. In anotherembodiment, FES control can be used to position the agonist/antagonistmuscles within the Pro-m-RPNI 176 to reflect measured joint positions ofthe bionic limb into actual fascicle states of the agonist/antagonistmuscles. Generally, such a FES control would occur when, for example, anexternal agent positions the bionic limb joint, such as during a handshake, or when the bionic leg strikes the ground surface in awalking/running stride, causing the bionic leg joints to rotate.

Another microprocessor, called the Sensory controller 184 in FIG. 20,located within the bionic limb maps measured strain sensory signals fromthe synthetic skin of the prosthetic hand into FES control commandsapplied to the muscle(s) of implanted Cut-s-RPNI(s) 178. To provide asimple example, we assume that each finger digit corresponds to oneunidirectional Cut-s-RPNI 178 (See FIG. 18). When the bionic hand graspsthe bar bell, the measured orthogonal strain on each syntheticfingertip, or pressure, is converted by the sensory controller 184 intoa corresponding cutaneous FES control command. The muscle of thecorresponding unidirectional Cut-s-RPNI 178 then contracts and applies aunidirectional tensile strain on the biological skin patch. Because theskin patch wraps around a curved surface, as in FIG. 18, the appliedtensile shear also causes an orthogonal shear to be applied to the skinpatch, or a pressure. With the coupling between tensile strain andorthogonal strain (pressure) known, the FES on the Cut-s-RPNI 178 muscleis modulated in a closed-loop manner until the measured muscle strain,determined from sonomicrometer crystals implanted within the Cut-s-RPNI178 muscle, is equal to a target tensile skin strain and a targetpressure. The nerve innervating the skin patch then communicates anafferent signal via the skin mechanoreceptors, providing a naturalcutaneous feedback into the nervous system and allowing the prostheticuser to better manipulate objects of interest such as the bar bell. Thespool shape in FIG. 18, or the sphere shape in FIG. 19, can be adjustedto modulate the relationship between skin tensile shear and orthogonalshear (pressure). Although circular cross sections are shown in FIGS. 18and 19, more of a point pressure may be sought when a tensile strain isapplied to the skin patch, necessitating a non-circular cross sectionsuch as an ellipse.

The relevant teachings of all patents, published applications andreferences cited herein are incorporated by reference in their entirety.

While this invention has been particularly shown and described withreferences to example embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the inventionencompassed by the appended claims.

1. A method of restoring at least partial function of a human limb,comprising the steps of: a) surgically removing at least a portion of aninjured or diseased human limb from a surgical site of an individual,leaving intact at least one selected muscle from the removed portion ofthe human limb, including at least one of blood vessels and nervesassociated with the at least one selected muscle; b) transplanting theat least one selected muscle into the remaining biological body of theindividual; and c) contacting, directly or indirectly, the at least onetransplanted selected muscle, or associated nerve, with an electrode,whereby signals can be transmitted to and from at least one of the nerveand its associated transplanted muscle to thereby control a devicelinked to the electrode and extending from the surgical site, therebyrestoring at least partial function of the human limb. 2-23. (canceled)24. A method of reversing impairment of a human limb, comprising thesteps of: a) transecting a nerve associated with the impairment of thelimb of an individual to thereby form proximal and distal ends of thetransected nerve; b) placing the proximal and distal ends of thetransected nerve into proximal and distal ends of a microchannel array,thereby causing the nerve to regenerate through the microchannel array;c) recording sensory afferent information of the regenerated nerve usingsensing electrodes within a plurality of afferent microchannels of themicrochannel array; d) stimulating motor efferent information to provideefferent motor stimulus to the nerve using stimulating electrodes withina plurality of efferent microchannels of the microchannel array; e)electrically connecting the stimulating electrodes to a motor controllerof a device; and f) electrically connecting the sensing electrodes to asensory controller of the device, wherein the sensory controller islinked to at least one sensor of the biological limb that detectsapplication of at least one of position, velocity, acceleration, andforce of the biological limb, and whereby the sensory controllertransmits detection of the position, velocity, acceleration, and forceof the biological limb to the motor controller, and whereby the motorcontroller applies electrical stimulation via the stimulatingelectrodes, thereby reversing impairment of the human limb. 25-28.(canceled)
 29. A method of restoring at least partial function of ahuman limb an individual, comprising the steps of: a) dissecting atleast one patch of skin from the individual; b) translocating the patchof skin onto a non-anatomical portion of the individual, wherein theskin patch includes at least one nerve selected from the groupconsisting of an intact native nerve and a new regenerative innervationnerve; and c) contacting the translocated skin patch with an externaldevice, the device including at least one component that providesmechanical stimulation to the translocated skin patch, thereby restoringat least partial function of the human limb.
 30. A method of reversingimpairment of an amputated limb, comprising the steps of: a) inserting adistal end of at least one transected nerve of an amputated limb into aproximal end of a microchannel array; b) placing at least one member ofthe group consisting of skin and muscle end organs at a distal end ofthe microchannel array, thereby causing the nerve to regenerate throughthe microchannel array and to innervate the at least one end organ; c)recording efferent motor information of the regenerated nerve usingsensing electrodes within a plurality of efferent microchannels of themicrochannel array; d) stimulating the regenerated nerve with afferentsensory information using stimulating electrodes within a plurality ofafferent microchannels of the microchannel array; e) electricallyconnecting the sensing electrodes to a motor controller of a device; andf) electrically connecting the stimulating electrodes to a sensorycontroller of the device, wherein the motor controller is linked to atleast one sensor of the device that detects application of at least onemember selected from the group consisting of position, velocity,acceleration, and force of the device, and whereby the motor controllertransmits detection of the position, velocity, acceleration, and forceby applying electrical stimulation via the stimulating electrodes,thereby providing the individual with a sensation simulating sensoryfeedback from the device, and reversing impairment of the amputatedlimb.
 31. (canceled)
 32. A method for neurally controlling a device,comprising the steps of: a) mechanically linking at least one pair ofagonist and antagonist muscles, wherein a nerve innervates each muscle;b) supporting the at least one pair of agonist and antagonist muscleswith a support, whereby contraction of the agonist muscle of each pairwill cause extension of the paired antagonist muscle; c) implanting atleast one electrode in at least one muscle of each pair; and d)electrically connecting the at least one electrode to a motor controllerof a device, thereby neurally controlling the device.
 33. The method ofclaim 32, wherein at least one of the innervated agonist and antagonistmuscles includes at least one member selected from the group consistingof a Golgi tendon organ, muscle spindle stretch fibers, an efferentnerve fiber and an afferent nerve fiber.
 34. The method of claim 33,wherein at least one of the muscles includes a Golgi tendon organ andthe other of the muscles includes spindle stretch fibers, wherein theGolgi tendon organs and the spindle stretch fibers generate afferentsignals.
 35. The method of claim 32, wherein the at least one electrodein the at least one muscle of each pair senses muscle activation orartificially stimulates and thereby causes muscle contraction.
 36. Themethod of claim 35, wherein a position about a degree of freedom of thedevice can be sensed by an individual wearing the device, the agonistand antagonist muscles simulating a proprioceptive sensory feedback tothe individual.
 37. The method of claim 32, wherein the device is awearable device.
 38. The method of claim 37, wherein the wearable deviceincludes at least one member selected from the group consisting of aprosthesis, orthosis or exoskeleton.
 39. The method of claim 32, whereinthe nerve includes at least one member selected from the groupconsisting of a regenerative nerve and a native nerve.
 40. The method ofclaim 32, further including the step of mechanically linking a pluralityof pairs of agonist and antagonist muscles for controlling of at leastone degree of freedom of the device.
 41. The method of claim 32, furtherincluding the step of associating a plurality of pairs of electrodes,each pair of electrodes being electrically connected to a pair ofagonist and antagonist muscles, with a plurality of degrees of freedomof the device, each degree of freedom of the device being associatedwith at least one pair of electrodes of an agonist/antagonist musclepair.
 42. The method of claim 32, wherein at least one pair of thelinked agonist/antagonist muscles is supported by a biologicalstructure.
 43. The method of claim 32, wherein the biological structureis a human bone.
 44. The method of claim 32, wherein at least one pairof the linked antagonist/antagonist muscles is supported by anartificial support.
 45. The method of claim 44, wherein theagonist/antagonist muscles of the pair are linked linearly to each otherat one end, and linked at their respective free ends to the artificialsupport.
 46. The method of claim 45, wherein at least one of therespective free ends of the agonist/antagonist muscle pair includesnative bone, which bone is secured to the artificial support.
 47. Themethod of claim 46, wherein the agonist/antagonist muscles of the pairis linked to each other by the artificial support.
 48. The method ofclaim 47, wherein the artificial support is a lever, in which one end ofeach muscle is attached to an arm, the arms being on opposite sides of afulcrum of the lever, whereby contraction of one muscle of theagonist/antagonist pair causes extension of the other muscle of theagonist/antagonist pair.
 49. The method of claim 32, wherein the ends ofeach agonist/antagonist muscle pair are linked to each other to form aclosed loop, and wherein the muscle extends about a periphery of thesupport, whereby contraction of one of the muscles of the pair willcause extension of the other muscle of the pair.
 50. The method of claim32, further including the step of implanting in at least oneagonist/antagonist muscle pair at least one member of the groupconsisting of a force sensor and a position sensor.
 51. The method ofclaim 50, wherein the position sensor includes a plurality ofpiezoelectric crystals.
 52. The method of claim 51, wherein thepiezoelectric crystals include sonomicrometry crystals.
 53. The methodof claim 52, wherein the relative positions of the implanted crystalsare employed to establish a control target of at least one of speed andlength of at least one of the muscles of the agonist/antagonist musclepair by the motor controller and thereby estimate the joint state of thedevice to control the device with the motor controller.
 54. The methodof claim 53, wherein estimating the joint state further includes thesteps of measuring with the force sensor the force applied by the leastone of the muscles of the agonist/antagonist muscle pair, and combiningthat measurement with the measurements of speed and length of thecorresponding muscles of the muscle pair.
 55. The method of claim 54,wherein the force sensor includes at least one of a strain gauge and aforce buckle.
 56. The method of claim 50, wherein the motor controlleremploys the strength of an electromyographic sensory signal measuredwith the electrode at the agonist/antagonist muscle pair, and positionand speed of the agonist/antagonist muscle pair measured with theposition sensor, to estimate joint state and torque of the device. 57.The method of claim 32, wherein the device is selected from the groupconsisting of a prosthesis, an orthosis and an exoskeleton, and whereinthe motor controller detects motion in the prosthesis, orthosis orexoskeleton, and relays that information by selectively stimulating viathe electrode at least one muscle of the agonist/antagonist pair,thereby causing an individual wearing the prosthesis, orthosis orexoskeleton to sense the change in position of the prosthesis, orthosisor exoskeleton.
 58. A method for simulating cutaneous sensory feedbackfrom a device, comprising the steps of: a) excising a skin segment froma biological body part of an individual, the skin segment including atleast one of a native nerve and a regenerative nerve supply; b) linkingthe skin segment with at least one muscle having a nerve supply; c)implanting an electrode in the at least one muscle; d) supporting theskin segment and at least one muscle on a support; and e) electricallyconnecting the at least one electrode to a sensory controller of adevice, wherein the controller is linked to a sensor of the device thatdetects application of at least one of stress, strain, contact, pressureand shear at the device, and whereby the controller transmits detectionof the stress, strain, contact, pressure or shear by contracting the atleast one muscle with an electrical stimulation via the electrode,thereby stretching a mechanoreceptor of the skin segment and providingthe individual with a sensation simulating cutaneous sensory feedbackfrom the device. 59-75. (canceled)
 76. The method of claim 56, whereinplural electrodes are implanted, at least one electrode in each of themuscles of the agonist/antagonist muscle pair, the motor controlleremploying electromygraphic signals measured with the electrodes toacquire motor intent of an individual wearing the device.
 77. The methodof claim 76, wherein the device is selected from the group consisting ofa prosthesis, an orthosis and an exoskeleton, the motor controlleremploying the level of common mode of the electromyographic signalsmeasured by the electrodes on the agonist/antagonist muscle pair todetermine impedance of a joint of the prosthesis, orthosis orexoskeleton according to the individual's motor intent.
 78. The methodof claim 77, wherein the motor controller further employs the level ofdifferential mode of the electromyographic signals measured by theelectrodes on the agonist/antagonist pair to determine position andspeed of the joint of the prosthesis, orthosis or exoskeleton accordingto the individual's motor intent.
 79. The method of claim 78, whereinthe motor controller maps, using a biomimetic model of a human limb, themeasured electromyographic signals and position and speed of theagonist/antagonist muscle pair to control targets for torque, impedanceand joint state of the joint of the prosthesis, orthosis or exoskeleton.80. The method of claim 79, wherein the motor controller includes aclosed-loop controller to servo to the targets, to thereby control thedevice according to the individual's motor intent.